{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:20:25Z","timestamp":1785439225083,"version":"3.56.0"},"reference-count":330,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,28]],"date-time":"2024-09-28T00:00:00Z","timestamp":1727481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Cardiovascular disease is a leading cause of morbidity and mortality. New research elucidates increasingly complex relationships between cardiac and metabolic health, giving rise to new possible therapeutic targets. Sphingolipids are a heterogeneous class of bioactive lipids with critical roles in normal human physiology. They have also been shown to play both protective and deleterious roles in the pathogenesis of cardiovascular disease. Ceramides are implicated in dysregulating insulin signalling, vascular endothelial function, inflammation, oxidative stress, and lipoprotein aggregation, thereby promoting atherosclerosis and vascular disease. Ceramides also advance myocardial disease by enhancing pathological cardiac remodelling and cardiomyocyte death. Glucosylceramides similarly contribute to insulin resistance and vascular inflammation, thus playing a role in atherogenesis and cardiometabolic dysfunction. Sphingosing-1-phosphate, on the other hand, may ameliorate some of the pathological functions of ceramide by protecting endothelial barrier integrity and promoting cell survival. Sphingosine-1-phosphate is, however, implicated in the development of cardiac fibrosis. This review will explore the roles of sphingolipids in vascular, cardiac, and metabolic pathologies and will evaluate the therapeutic potential in targeting sphingolipids with the aim of prevention and reversal of cardiovascular disease in order to improve long-term cardiovascular outcomes.<\/jats:p>","DOI":"10.3390\/nu16193296","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T05:45:27Z","timestamp":1727675127000},"page":"3296","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Emerging Roles for Sphingolipids in Cardiometabolic Disease: A Rational Therapeutic Target?"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1335-8576","authenticated-orcid":false,"given":"Daniel","family":"Foran","sequence":"first","affiliation":[{"name":"Cardiovascular Medicine Division, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charalambos","family":"Antoniades","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Division, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Akoumianakis","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Division, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/j.jacc.2022.11.005","article-title":"The Global Burden of Cardiovascular Diseases and Risk: A Compass for Future Health","volume":"80","author":"Vaduganathan","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Emerging Risk Factors Collaboration, Sarwar, N., Gao, P., Seshasai, S.R.K., Gobin, R., Kaptoge, S., Di Angelantonio, E., Lawlor, D.A., Selvin, E., and Stampfer, M. (2010). Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: A collaborative meta-analysis of 102 prospective studies. Lancet, 375, 2215\u20132222.","DOI":"10.1016\/S0140-6736(10)60484-9"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41569-021-00536-1","article-title":"Ceramides and other sphingolipids as drivers of cardiovascular disease","volume":"18","author":"Choi","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1006\/taap.1996.8029","article-title":"Sphingolipids\u2014The Enigmatic Lipid Class: Biochemistry, Physiology, and Pathophysiology","volume":"142","author":"Merrill","year":"1997","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrm.2017.107","article-title":"Sphingolipids and their metabolism in physiology and disease","volume":"19","author":"Hannun","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Merrill, A.H. (2013). Lipids Carbohydrates Membranes and Membrane Proteins\u2014Sphingolipid Biosynthesis. Encyclopedia of Biological Chemistry, Elsevier. [2nd ed.].","DOI":"10.1016\/B978-0-12-378630-2.00515-6"},{"key":"ref_7","first-page":"1","article-title":"An overview of sphingolipid metabolism: From synthesis to breakdown","volume":"Volume 688","author":"Gault","year":"2010","journal-title":"Sphingolipids as Signaling and Regulatory Molecules. Advances in Experimental Medicine and Biology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/0009-3084(70)90008-3","article-title":"On the chemistry and occurrence of sphingolipid long-chain bases\u2014ScienceDirect","volume":"5","author":"Karlsson","year":"1970","journal-title":"Chem. Phys. Lipids"},{"key":"ref_9","first-page":"589","article-title":"Cellular and molecular biology of glycosphingolipid glycosylation","volume":"117","author":"Maccioni","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.chemphyslip.2018.09.013","article-title":"Visualizing bioactive ceramides","volume":"216","author":"Canals","year":"2018","journal-title":"Chem. Phys. Lipids"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Quinville, B.M., Deschenes, N.M., Ryckman, A.E., and Walia, J.S. (2021). A Comprehensive Review: Sphingolipid Metabolism and Implications of Disruption in Sphingolipid Homeostasis. Int. J. Mol. Sci., 22, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8198874\/.","DOI":"10.3390\/ijms22115793"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1016\/j.bbamem.2006.08.009","article-title":"Ceramides and other bioactive sphingolipid backbones in health and disease: Lipidomic analysis, metabolism and roles in membrane structure, dynamics, signaling and autophagy","volume":"1758","author":"Zheng","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1194\/jlr.R800012-JLR200","article-title":"Thematic Review Series: Sphingolipids. Biodiversity of sphingoid bases (\u201csphingosines\u201d) and related amino alcohols","volume":"49","author":"Pruett","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0022-2275(20)37838-X","article-title":"Utilization of different fatty acyl-CoA thioesters by serine palmitoyltransferase from rat brain","volume":"25","author":"Merrill","year":"1984","journal-title":"J. Lipid Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.jchromb.2007.02.030","article-title":"Separation and mass spectrometric characterization of covalently bound skin ceramides using LC\/APCI-MS and Nano-ESI-MS\/MS","volume":"852","author":"Farwanah","year":"2007","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41375-021-01378-z","article-title":"3-Ketodihydrosphingosine reductase maintains ER homeostasis and unfolded protein response in leukemia","volume":"36","author":"Liu","year":"2021","journal-title":"Leukemia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1194\/jlr.S092874","article-title":"Advances in determining signaling mechanisms of ceramide and role in disease","volume":"60","author":"Stith","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4222","DOI":"10.1172\/JCI57144","article-title":"Ceramides as modulators of cellular and whole-body metabolism","volume":"121","author":"Bikman","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/tra.12239","article-title":"Sphingolipid Metabolism and Interorganellar Transport: Localization of Sphingolipid Enzymes and Lipid Transfer Proteins","volume":"16","author":"Yamaji","year":"2014","journal-title":"Traffic"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.plipres.2016.03.006","article-title":"The enigma of ceramide synthase regulation in mammalian cells","volume":"63","author":"Wegner","year":"2016","journal-title":"Prog. Lipid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"22432","DOI":"10.1074\/jbc.272.36.22432","article-title":"Characterization of ceramide synthesis. A dihydroceramide desaturase introduces the 4,5-trans-double bond of sphingosine at the level of dihydroceramide","volume":"272","author":"Michel","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_23","first-page":"704","article-title":"Co-evolution of sphingomyelin and the ceramide transport protein CERT","volume":"1841","author":"Hanada","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6387","DOI":"10.1021\/cr2002917","article-title":"Sphingolipid and Glycosphingolipid Metabolic Pathways in the Era of Sphingolipidomics","volume":"111","author":"Merrill","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_25","unstructured":"Lennarz, W.J., and Lane, D. (2013). Sphingolipid Catabolism. Encyclopedia of Biological Chemistry, Elsevier. [2nd ed.]."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"454","DOI":"10.2174\/156652410791608225","article-title":"The Acid Sphingomyelinase\/Ceramide Pathway: Biomedical Significance and Mechanisms of Regulation","volume":"10","author":"Zeidan","year":"2010","journal-title":"Curr. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Boer, D.E., van Smeden, J., Bouwstra, J.A., and Aerts, J.M. (2020). Glucocerebrosidase: Functions in and Beyond the Lysosome. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030736"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.cellsig.2007.12.006","article-title":"The sphingolipid salvage pathway in ceramide metabolism and signaling","volume":"20","author":"Kitatani","year":"2007","journal-title":"Cell. Signal."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1042\/BJ20071240","article-title":"Sphingomyelin synthases regulate production of diacylglycerol at the Golgi","volume":"414","author":"Villani","year":"2008","journal-title":"Biochem. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/sj.emboj.7600034","article-title":"Identification of a family of animal sphingomyelin synthases","volume":"23","author":"Huitema","year":"2004","journal-title":"EMBO J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0005-2760(90)90211-F","article-title":"An update of the enzymology and regulation of sphingomyelin metabolism","volume":"1044","author":"Merrill","year":"1990","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_32","unstructured":"Varki, A., Cummings, R., Esko, J., Freeze, H., Hart, G., and Marth, J. (1999). Chapter 9: Glycosphingolipids. Essentials of Glycobiology, Cold Spring Harbor Laboratory Press."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/nature06097","article-title":"Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide","volume":"449","author":"Polishchuk","year":"2007","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"25880","DOI":"10.1074\/jbc.273.40.25880","article-title":"UDP-Galactose:Ceramide Galactosyltransferase Is a Class I Integral Membrane Protein of the Endoplasmic Reticulum","volume":"273","author":"Sprong","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"23294","DOI":"10.1074\/jbc.M201535200","article-title":"Ceramide kinase, a novel lipid kinase. Molecular cloning and functional characterization","volume":"277","author":"Sugiura","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature12332","article-title":"Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates eicosanoids","volume":"500","author":"Simanshu","year":"2013","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"109980","DOI":"10.1016\/j.cellsig.2021.109980","article-title":"Regulation of cell growth, survival and migration by ceramide 1-phosphate\u2014Implications in lung cancer progression and inflammation","volume":"83","author":"Ouro","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1111\/j.1471-4159.1993.tb07470.x","article-title":"Ceramide 1-Phosphate Phosphatase Activity in Brain","volume":"61","author":"Shinghal","year":"1993","journal-title":"J. Neurochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"16506","DOI":"10.1074\/jbc.271.28.16506","article-title":"Phosphatidate Phosphohydrolase Catalyzes the Hydrolysis of Ceramide 1-Phosphate, Lysophosphatidate, and Sphingosine 1-Phosphate","volume":"271","author":"Waggoner","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0090-6980(01)00103-4","article-title":"Sphingosine 1-phosphate: Synthesis and release","volume":"64","author":"Yatomi","year":"2001","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/jlb.65.3.341","article-title":"Sphingosine 1-phosphate: A prototype of a new class of second messengers","volume":"65","author":"Spiegel","year":"1999","journal-title":"J. Leukoc. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1111\/jnc.14703","article-title":"Extracellular and intracellular sphingosine-1-phosphate distinctly regulates exocytosis in chromaffin cells","volume":"149","author":"Jiang","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/978-1-4419-6741-1_10","article-title":"Extracellular and intracellular actions of sphingosine-1-phosphate","volume":"688","author":"Strub","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1042\/BJ20060251","article-title":"Extracellular export of sphingosine kinase-1a contributes to the vascular S1P gradient","volume":"397","author":"Venkataraman","year":"2006","journal-title":"Biochem. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"13341","DOI":"10.1016\/S0021-9258(18)33453-7","article-title":"Calcium-activated, phospholipid-dependent protein kinase from rat brain. Subcellular distribution, purification, and properties","volume":"257","author":"Kikkawa","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0076-6879(00)11086-9","article-title":"Analysis of ceramide 1-phosphate and sphingosine-1-phosphate phosphatase activities","volume":"311","author":"Brindley","year":"2000","journal-title":"Methods Enzymol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.bbrc.2004.10.036","article-title":"Sphingosine-1-phosphate lyase SPL is an endoplasmic reticulum-resident, integral membrane protein with the pyridoxal 5\u2032-phosphate binding domain exposed to the cytosol","volume":"325","author":"Ikeda","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100988","DOI":"10.1016\/j.plipres.2019.100988","article-title":"Mammalian sphingoid bases: Biophysical, physiological and pathological properties","volume":"75","author":"Carreira","year":"2019","journal-title":"Prog. Lipid Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0009-3084(93)90037-4","article-title":"Influence of sphingosine on the thermal phase behaviour of neutral and acidic phospholipid liposomes","volume":"66","author":"Mustonen","year":"1993","journal-title":"Chem. Phys. Lipids"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Carreira, A.C., de Almeida, R.F.M., and Silva, L.C. (2017). Development of lysosome-mimicking vesicles to study the effect of abnormal accumulation of sphingosine on membrane properties. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-04125-6"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3074","DOI":"10.1074\/jbc.M116.762377","article-title":"Sphingosine and Sphingosine Kinase 1 Involvement in Endocytic Membrane Trafficking","volume":"292","author":"Lima","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1126\/science.3101176","article-title":"Lysosphingolipids Inhibit Protein Kinase C: Implications for the Sphingolipidoses","volume":"235","author":"Hannun","year":"1987","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Miao, L.-N., Pan, D., Shi, J., Du, J.-P., Chen, P.-F., Gao, J., Yu, Y., Shi, D.-Z., and Guo, M. (2022). Role and Mechanism of PKC-\u03b4 for Cardiovascular Disease: Current Status and Perspective. Front. Cardiovasc. Med., 9, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8885814\/.","DOI":"10.3389\/fcvm.2022.816369"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"11549","DOI":"10.1074\/jbc.M609424200","article-title":"Activation of Acid Sphingomyelinase by Protein Kinase C\u03b4-mediated Phosphorylation","volume":"282","author":"Zeidan","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7747","DOI":"10.1021\/bi00245a011","article-title":"Inhibition of the insulin receptor tyrosine kinase by sphingosine","volume":"30","author":"Arnold","year":"1991","journal-title":"Biochemistry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"24434","DOI":"10.1073\/pnas.2007856117","article-title":"Regulation of hepatic insulin signaling and glucose homeostasis by sphingosine kinase 2","volume":"117","author":"Aji","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"eaav8824","DOI":"10.1126\/scitranslmed.aav8824","article-title":"Insulin-induced vascular redox dysregulation in human atherosclerosis is ameliorated by dipeptidyl peptidase 4 inhibition","volume":"12","author":"Akoumianakis","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1080\/15216540600871118","article-title":"Sphingosine and ceramide signalling in apoptosis","volume":"58","author":"Woodcock","year":"2006","journal-title":"IUBMB Life"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5457","DOI":"10.1128\/MCB.18.9.5457","article-title":"Regulation of Insulin-Stimulated Glucose Transporter GLUT4 Translocation and Akt Kinase Activity by Ceramide","volume":"18","author":"Summers","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"17402","DOI":"10.1073\/pnas.0802781105","article-title":"Ceramide starves cells to death by downregulating nutrient transporter proteins","volume":"105","author":"Guenther","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s10863-005-6567-7","article-title":"Mitochondrial Ceramide and the Induction of Apoptosis","volume":"37","author":"Siskind","year":"2005","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_62","first-page":"105","article-title":"AKT signaling in physiology and disease","volume":"347","author":"Vasudevan","year":"2010","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S1044-7431(02)00028-3","article-title":"Ceramide-induced neuronal apoptosis is associated with dephosphorylation of Akt, BAD, FKHR, GSK-3beta, and induction of the mitochondrial-dependent intrinsic caspase pathway","volume":"22","author":"Stoica","year":"2003","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"20296","DOI":"10.1074\/jbc.274.29.20296","article-title":"Ceramide induces Bcl2 dephosphorylation via a mechanism involving mitochondrial PP2A","volume":"274","author":"Ruvolo","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1194\/jlr.R031278","article-title":"Sphingolipids: Regulators of crosstalk between apoptosis and autophagy","volume":"54","author":"Young","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"15371","DOI":"10.1074\/jbc.R115.653204","article-title":"Dihydroceramides: From Bit Players to Lead Actors","volume":"290","author":"Siddique","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.bbagen.2016.11.033","article-title":"Dihydroceramide desaturase inhibitors induce autophagy via dihydroceramide-dependent and independent mechanisms","volume":"1861","author":"Casasampere","year":"2017","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"26226","DOI":"10.1016\/S0021-9258(19)74304-X","article-title":"Selectivity of ceramide-mediated biology. Lack of activity of erythro-dihydroceramide","volume":"268","author":"Bielawska","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"38640","DOI":"10.1074\/jbc.C000587200","article-title":"The Lipids C2- and C16-Ceramide Form Large Stable Channels","volume":"275","author":"Siskind","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1016\/j.biocel.2012.08.025","article-title":"Dihydroceramide delays cell cycle G1\/S transition via activation of ER stress and induction of autophagy","volume":"44","author":"Gagliostro","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2165\/00128071-200304020-00004","article-title":"Ceramides and skin function","volume":"4","author":"Coderch","year":"2003","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_72","first-page":"287","article-title":"The two compartment model of the stratum corneum: Biochemical aspects and pathophysiological implications","volume":"68","author":"Hachem","year":"2006","journal-title":"Verh. K. Acad. Voor Geneeskd. Van Belg."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1074\/jbc.M610304200","article-title":"Integrity and Barrier Function of the Epidermis Critically Depend on Glucosylceramide Synthesis","volume":"282","author":"Jennemann","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1172\/JCI115439","article-title":"Sphingolipids are required for mammalian epidermal barrier function. Inhibition of sphingolipid synthesis delays barrier recovery after acute perturbation","volume":"88","author":"Holleran","year":"1991","journal-title":"J. Clin. Investig."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.bbalip.2013.12.003","article-title":"The role of sphingomyelin and sphingomyelin synthases in cell death, proliferation and migration-from cell and animal models to human disorders","volume":"1841","author":"Taniguchi","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.bbrc.2022.08.074","article-title":"Sphingomyelin: What is it good for?","volume":"633","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Subathra, M., Qureshi, A., and Luberto, C. (2011). Sphingomyelin Synthases Regulate Protein Trafficking and Secretion. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023644"},{"key":"ref_78","first-page":"87","article-title":"Effect of sphingomyelin and antioxidants on the in vitro and in vivo DNA methylation","volume":"35","author":"Romanenko","year":"1995","journal-title":"Biochem. Mol. Biol. Int."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"6529","DOI":"10.3390\/ijms14046529","article-title":"Nuclear Lipid Microdomain as Place of Interaction between Sphingomyelin and DNA during Liver Regeneration","volume":"14","author":"Albi","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"17537","DOI":"10.1074\/jbc.M702423200","article-title":"Both Sphingomyelin Synthases SMS1 and SMS2 Are Required for Sphingomyelin Homeostasis and Growth in Human HeLa Cells","volume":"282","author":"Tafesse","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"14636","DOI":"10.1074\/jbc.271.24.14636","article-title":"Complete Removal of Sphingolipids from the Plasma Membrane Disrupts Cell to Substratum Adhesion of Mouse Melanoma Cells","volume":"271","author":"Hidari","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Poitelon, Y., Kopec, A.M., and Belin, S. (2020). Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism. Cells, 9, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7226731\/.","DOI":"10.3390\/cells9040812"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1146\/annurev.bb.14.060185.002045","article-title":"Organization of glycosphingolipids in bilayers and plasma membranes of mammalian cells","volume":"14","author":"Thompson","year":"1985","journal-title":"Annu. Rev. Biophys. Biophys. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1038\/s41467-019-10711-1","article-title":"The role of PS 18:0\/18:1 in membrane function","volume":"10","author":"Skotland","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1194\/jlr.M200232-JLR200","article-title":"Glucosylceramide modulates membrane traffic along the endocytic pathway","volume":"43","author":"Sillence","year":"2002","journal-title":"J. Lipid Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1093\/jb\/mvr058","article-title":"Up-regulation of ceramide glucosyltransferase during the differentiation of U937 cells","volume":"150","author":"Aida","year":"2011","journal-title":"J. Biochem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.2353\/ajpath.2009.080841","article-title":"\u03b2-Glycoglycosphingolipid-Induced Alterations of the STAT Signaling Pathways Are Dependent on CD1d and the Lipid Raft Protein Flotillin-2","volume":"174","author":"Lalazar","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1136\/gut.2006.095497","article-title":"-Glucosylceramide: A novel method for enhancement of natural killer T lymphoycte plasticity in murine models of immune-mediated disorders","volume":"56","author":"Zigmond","year":"2007","journal-title":"Gut"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1182\/blood.V97.7.1907","article-title":"Plasma glucosylceramide deficiency as potential risk factor for venous thrombosis and modulator of anticoagulant protein C pathway","volume":"97","author":"Deguchi","year":"2001","journal-title":"Blood"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"19530","DOI":"10.1074\/jbc.271.32.19530","article-title":"Accumulation of Glucosylceramides in Multidrug-resistant Cancer Cells","volume":"271","author":"Lavie","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Messner, M.C., and Cabot, M.C. (2011). Glucosylceramide in Humans. Sphingolipids as Signaling and Regulatory Molecules, Springer.","DOI":"10.1007\/978-1-4419-6741-1_11"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1194\/jlr.M300486-JLR200","article-title":"Oligonucleotides blocking glucosylceramide synthase expression selectively reverse drug resistance in cancer cells","volume":"45","author":"Liu","year":"2004","journal-title":"J. Lipid Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1074\/jbc.M113.522847","article-title":"Ceramides and Glucosylceramides Are Independent Antagonists of Insulin Signaling","volume":"289","author":"Chavez","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1152\/physiol.00016.2009","article-title":"Oligodendrocyte Development and Myelin Biogenesis: Parsing Out the Roles of Glycosphingolipids","volume":"24","author":"Jackman","year":"2009","journal-title":"Physiology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/978-1-4939-1154-7_12","article-title":"Role of galactosylceramide and sulfatide in oligodendrocytes and CNS myelin: Formation of a glycosynapse","volume":"9","author":"Boggs","year":"2014","journal-title":"Adv. Neurobiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nri1531","article-title":"Alpha-Galactosylceramide therapy for autoimmune diseases: Prospects and obstacles","volume":"5","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/978-3-7091-1368-4_8","article-title":"The Role of Ceramide-1-Phosphate in Biological Functions","volume":"Volume 215","author":"Hoeferlin","year":"2013","journal-title":"Handbook of Experimental Pharmacology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1194\/jlr.M300158-JLR200","article-title":"Ceramide-1-phosphate blocks apoptosis through inhibition of acid sphingomyelinase in macrophages","volume":"45","author":"Kong","year":"2004","journal-title":"J. Lipid Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1042\/bj3250435","article-title":"Stimulation of DNA synthesis by natural ceramide 1-phosphate","volume":"325","author":"Frago","year":"1997","journal-title":"Biochem. J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.cellsig.2007.12.008","article-title":"Ceramide 1-phosphate stimulates macrophage proliferation through activation of the PI3-kinase\/PKB, JNK and ERK1\/2 pathways","volume":"20","author":"Gangoiti","year":"2007","journal-title":"Cell. Signal."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.cellsig.2008.11.003","article-title":"Ceramide 1-phosphate (C1P) promotes cell migration","volume":"21","author":"Granado","year":"2008","journal-title":"Cell. Signal."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"11320","DOI":"10.1074\/jbc.M309262200","article-title":"Ceramide 1-Phosphate Is a Direct Activator of Cytosolic Phospholipase A2","volume":"279","author":"Pettus","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"42808","DOI":"10.1074\/jbc.M111.310169","article-title":"Ceramide Kinase Regulates the Production of Tumor Necrosis Factor \u03b1 (TNF\u03b1) via Inhibition of TNF\u03b1-converting Enzyme","volume":"286","author":"Lamour","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e927","DOI":"10.1038\/cddis.2013.455","article-title":"Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of Bim and PI-3-kinase\/protein kinase C-mediated upregulation of Mcl-1","volume":"4","author":"Rutherford","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41420-023-01681-x","article-title":"The role of sphingosine-1-phosphate in autophagy and related disorders","volume":"9","author":"Xiao","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev-immunol-020711-075011","article-title":"Sphingosine-1-Phosphate and Lymphocyte Egress from Lymphoid Organs","volume":"30","author":"Cyster","year":"2012","journal-title":"Annu. Rev. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.cmet.2012.06.017","article-title":"Sphingolipid Signaling in Metabolic Disorders","volume":"16","author":"Hla","year":"2012","journal-title":"Cell Metab."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"6299","DOI":"10.1021\/cr200273u","article-title":"Regulation of Mammalian Physiology, Development, and Disease by the Sphingosine 1-Phosphate and Lysophosphatidic Acid Receptors","volume":"111","author":"Blaho","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"ftw063","DOI":"10.1093\/femspd\/ftw063","article-title":"Sphingosine 1-phosphate signaling impacts lymphocyte migration, inflammation and infection","volume":"74","author":"Tiper","year":"2016","journal-title":"Pathog. Dis."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1126\/science.1139221","article-title":"Promotion of Lymphocyte Egress into Blood and Lymph by Distinct Sources of Sphingosine-1-Phosphate","volume":"316","author":"Pappu","year":"2007","journal-title":"Science"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1126\/science.1113640","article-title":"Lymphocyte Sequestration Through S1P Lyase Inhibition and Disruption of S1P Gradients","volume":"309","author":"Schwab","year":"2005","journal-title":"Science"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1042\/bj3520809","article-title":"Interaction of sphingosine 1-phosphate with plasma components, including lipoproteins, regulates the lipid receptor-mediated actions","volume":"352","author":"Murata","year":"2000","journal-title":"Biochem. J."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.devcel.2012.08.005","article-title":"The Sphingosine-1-Phosphate Receptor S1PR1 Restricts Sprouting Angiogenesis by Regulating the Interplay between VE-Cadherin and VEGFR2","volume":"23","author":"Gaengel","year":"2012","journal-title":"Dev. Cell"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.1016\/j.celrep.2019.11.036","article-title":"Sphingosine-1-Phosphate Receptor 1 Activity Promotes Tumor Growth by Amplifying VEGF-VEGFR2 Angiogenic Signaling","volume":"29","author":"Ragunathrao","year":"2019","journal-title":"Cell Rep."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1158\/0008-5472.CAN-05-2001","article-title":"Antagonism of Sphingosine-1-Phosphate Receptors by FTY720 Inhibits Angiogenesis and Tumor Vascularization","volume":"66","author":"LaMontagne","year":"2006","journal-title":"Cancer Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"C14","DOI":"10.1152\/ajpcell.00043.2014","article-title":"Host endothelial S1PR1 regulation of vascular permeability modulates tumor growth","volume":"307","author":"Sarkisyan","year":"2014","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"104793","DOI":"10.1016\/j.phrs.2020.104793","article-title":"Significance of sphingosine-1-phosphate in cardiovascular physiology and pathology","volume":"156","author":"Jozefczuk","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0092-8674(00)81661-X","article-title":"Vascular Endothelial Cell Adherens Junction Assembly and Morphogenesis Induced by Sphingosine-1-Phosphate","volume":"99","author":"Lee","year":"1999","journal-title":"Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"H363","DOI":"10.1152\/ajpheart.00687.2013","article-title":"Sphingosine-1-phosphate protects endothelial glycocalyx by inhibiting syndecan-1 shedding","volume":"306","author":"Zeng","year":"2014","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_120","first-page":"1871","article-title":"Sphingosine-1-phosphate in the plasma compartment regulates basal and inflammation-induced vascular leak in mice","volume":"119","author":"Camerer","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1172\/JCI10905","article-title":"Edg-1, the G protein\u2013coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation","volume":"106","author":"Liu","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3665","DOI":"10.1182\/blood-2003-02-0460","article-title":"G-protein-coupled receptor S1P1 acts within endothelial cells to regulate vascular maturation","volume":"102","author":"Allende","year":"2003","journal-title":"Blood"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1093\/intimm\/dxz037","article-title":"Sphingosine 1-phosphate and inflammation","volume":"31","author":"Obinata","year":"2019","journal-title":"Int. Immunol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"ra79","DOI":"10.1126\/scisignal.aaa2581","article-title":"HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation","volume":"8","author":"Galvani","year":"2015","journal-title":"Sci. Signal."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/1475-2840-13-82","article-title":"The compensatory enrichment of sphingosine -1- phosphate harbored on glycated high-density lipoprotein restores endothelial protective function in type 2 diabetes mellitus","volume":"13","author":"Tong","year":"2014","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Jebari-Benslaiman, S., Galicia-Garc\u00eda, U., Larrea-Sebal, A., Olaetxea, J.R., Alloza, I., Vandenbroeck, K., Benito-Vicente, A., and Mart\u00edn, C. (2022). Pathophysiology of Atherosclerosis. Int. J. Mol. Sci., 23, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8954705\/.","DOI":"10.3390\/ijms23063346"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e022852","DOI":"10.1161\/JAHA.121.022852","article-title":"Plasma Ceramide Levels Are Elevated in Patients with Early Coronary Atherosclerosis and Endothelial Dysfunction","volume":"11","author":"Akhiyat","year":"2022","journal-title":"J. Am. Hear. Assoc."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.atherosclerosis.2015.03.011","article-title":"Plasma C20-Sphingolipids predict cardiovascular events independently from conventional cardiovascular risk factors in patients undergoing coronary angiography","volume":"240","author":"Othman","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1161\/ATVBAHA.116.305675","article-title":"Sphingolipids Contribute to Human Atherosclerotic Plaque Inflammation","volume":"36","author":"Edsfeldt","year":"2016","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1093\/eurheartj\/ehw148","article-title":"Plasma ceramides predict cardiovascular death in patients with stable coronary artery disease and acute coronary syndromes beyond LDL-cholesterol","volume":"37","author":"Laaksonen","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1161\/ATVBAHA.118.311208","article-title":"nSMase2 (Type 2-Neutral Sphingomyelinase) Deficiency or Inhibition by GW4869 Reduces Inflammation and Atherosclerosis in Apoe \u2212\/\u2212 Mice","volume":"38","author":"Lallemand","year":"2018","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Piccoli, M., Cirillo, F., Ghiroldi, A., Rota, P., Coviello, S., Tarantino, A., La Rocca, P., Lavota, I., Creo, P., and Signorelli, P. (2023). Sphingolipids and Atherosclerosis: The Dual Role of Ceramide and Sphingosine-1-Phosphate. Antioxidants, 12.","DOI":"10.3390\/antiox12010143"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/978-3-7091-1511-4_9","article-title":"Cross talk between ceramide and redox signaling: Implications for endothelial dysfunction and renal disease","volume":"Volume 216","author":"Li","year":"2013","journal-title":"Handbook of Experimental Pharmacology"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"e2025347118","DOI":"10.1073\/pnas.2025347118","article-title":"Ceramide accumulation induces mitophagy and impairs \u03b2-oxidation in PINK1 deficiency","volume":"118","author":"Vos","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1159\/000315104","article-title":"Ceramide in Redox Signaling and Cardiovascular Diseases","volume":"26","author":"Li","year":"2010","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s10557-022-07378-0","article-title":"The Acid Sphingomyelinase Inhibitor Amitriptyline Ameliorates TNF-\u03b1-Induced Endothelial Dysfunction","volume":"38","author":"Ji","year":"2022","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1152\/ajplung.00385.2010","article-title":"Mechanisms of lung endothelial barrier disruption induced by cigarette smoke: Role of oxidative stress and ceramides","volume":"301","author":"Schweitzer","year":"2011","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.2337\/db11-1399","article-title":"Ceramide Mediates Vascular Dysfunction in Diet-Induced Obesity by PP2A-Mediated Dephosphorylation of the eNOS-Akt Complex","volume":"61","author":"Zhang","year":"2012","journal-title":"Diabetes"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1161\/HYPERTENSIONAHA.119.14507","article-title":"Endothelial Sphingolipid De Novo Synthesis Controls Blood Pressure by Regulating Signal Transduction and NO via Ceramide","volume":"75","author":"Cantalupo","year":"2020","journal-title":"Hypertension"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1515\/hsz-2014-0305","article-title":"The role of sphingolipids in endothelial barrier function","volume":"396","author":"Jernigan","year":"2015","journal-title":"Biol. Chem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1161\/01.CIR.0000035650.05921.50","article-title":"Dual effect of ceramide on human endothelial cells: Induction of oxidative stress and transcriptional upregulation of endothelial nitric oxide synthase","volume":"106","author":"Li","year":"2002","journal-title":"Circulation"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"9642","DOI":"10.1021\/la800714w","article-title":"Effect of Sphingomyelinase-Mediated Generation of Ceramide on Aggregation of Low-Density Lipoprotein","volume":"24","author":"Walters","year":"2008","journal-title":"Langmuir"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1194\/jlr.M023218","article-title":"Conformational changes of apoB-100 in SMase-modified LDL mediate formation of large aggregates at acidic pH","volume":"53","author":"Sneck","year":"2012","journal-title":"J. Lipid Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1093\/eurheartj\/ehy319","article-title":"Susceptibility of low-density lipoprotein particles to aggregate depends on particle lipidome, is modifiable, and associates with future cardiovascular deaths","volume":"39","author":"Ruuth","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"823071","DOI":"10.1155\/2014\/823071","article-title":"Endogenous Ceramide Contributes to the Transcytosis of oxLDL across Endothelial Cells and Promotes Its Subendothelial Retention in Vascular Wall","volume":"2014","author":"Li","year":"2014","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1053\/gast.2002.32539","article-title":"Dietary sphingomyelin suppresses intestinal cholesterol absorption by decreasing thermodynamic activity of cholesterol monomers","volume":"122","author":"Eckhardt","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.freeradbiomed.2012.05.026","article-title":"Palmitate promotes monocyte atherogenicity via de novo ceramide synthesis","volume":"53","author":"Gao","year":"2012","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.ejphar.2008.02.089","article-title":"Sphingolipid signalling in the cardiovascular system: Good, bad or both?","volume":"585","author":"Alewijnse","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s12944-022-01701-2","article-title":"Effects of sphingolipid metabolism disorders on endothelial cells","volume":"21","author":"Lai","year":"2022","journal-title":"Lipids Heal. Dis."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"S86","DOI":"10.1016\/j.placenta.2013.12.006","article-title":"Review: Novel insights into the regulation of vascular tone by sphingosine 1-phosphate","volume":"35","author":"Kerage","year":"2014","journal-title":"Placenta"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ejphar.2016.02.056","article-title":"Sphingosine-1-phosphate receptor 2 mediates endothelial cells dysfunction by PI3K-Akt pathway under high glucose condition","volume":"776","author":"Liu","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1152\/ajpcell.00014.2007","article-title":"Sphingosine 1-phosphate rapidly increases endothelial barrier function independently of VE-cadherin but requires cell spreading and Rho kinase","volume":"293","author":"Xu","year":"2007","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.bbadis.2018.12.022","article-title":"Sphingosine-1-phosphate promotes barrier-stabilizing effects in human microvascular endothelial cells via AMPK-dependent mechanisms","volume":"1865","author":"Dennhardt","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1016\/j.yexcr.2011.05.011","article-title":"Ceramide 1-phosphate induces neointimal formation via cell proliferation and cell cycle progression upstream of ERK1\/2 in vascular smooth muscle cells","volume":"317","author":"Kim","year":"2011","journal-title":"Exp. Cell Res."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0022-2275(20)36996-0","article-title":"Distribution of glycosphingolipids in the serum lipoproteins of normal human subjects and patients with hypo- and hyperlipidemias","volume":"17","author":"Dawson","year":"1976","journal-title":"J. Lipid Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1161\/ATVBAHA.109.201673","article-title":"Inhibition of Glycosphingolipid Synthesis Induces a Profound Reduction of Plasma Cholesterol and Inhibits Atherosclerosis Development in APOE*3 Leiden and Low-Density Lipoprotein Receptor\u2212\/\u2212 Mice","volume":"30","author":"Bietrix","year":"2010","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1161\/01.RES.82.5.540","article-title":"Lactosylceramide Stimulates Human Neutrophils to Upregulate Mac-1, Adhere to Endothelium, and Generate Reactive Oxygen Metabolites In Vitro","volume":"82","author":"Arai","year":"1998","journal-title":"Circ. Res."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/rth2.12018","article-title":"Low level of the plasma sphingolipid, glucosylceramide, is associated with thrombotic diseases","volume":"1","author":"Deguchi","year":"2017","journal-title":"Res. Pr. Thromb. Haemost."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/glycob\/7.1.57","article-title":"Accumulation of glycosphingolipids in human atherosclerotic plaque and unaffected aorta tissues","volume":"7","author":"Chatterjee","year":"1997","journal-title":"Glycobiology"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"13474","DOI":"10.1016\/S0021-9258(18)67043-7","article-title":"Regulation of synthesis of lactosylceramide and long chain bases in normal and familial hypercholesterolemic cultured proximal tubular cells","volume":"261","author":"Chatterjee","year":"1986","journal-title":"J. Biol. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Okrzeja, J., Karwowska, A., and B\u0142achnio-Zabielska, A. (2022). The Role of Obesity, Inflammation and Sphingolipids in the Development of an Abdominal Aortic Aneurysm. Nutrients, 14.","DOI":"10.3390\/nu14122438"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.jvs.2015.12.056","article-title":"Inflammatory cells, ceramides, and expression of proteases in perivascular adipose tissue adjacent to human abdominal aortic aneurysms","volume":"65","author":"Folkesson","year":"2016","journal-title":"J. Vasc. Surg."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"16521","DOI":"10.1074\/jbc.273.26.16521","article-title":"Involvement of de NovoCeramide Biosynthesis in Tumor Necrosis Factor-\u03b1\/Cycloheximide-induced Cerebral Endothelial Cell Death","volume":"273","author":"Xu","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/jcp.10464","article-title":"NO induced apoptosis of vascular smooth muscle cells accompanied by ceramide increase","volume":"199","author":"Pilane","year":"2003","journal-title":"J. Cell. Physiol."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Kasumov, T., Li, L., Li, M., Gulshan, K., Kirwan, J.P., Liu, X., Previs, S., Willard, B., Smith, J.D., and McCullough, A. (2015). Ceramide as a Mediator of Non-Alcoholic Fatty Liver Disease and Associated Atherosclerosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126910"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1183\/09031936.00080014","article-title":"Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation","volume":"45","author":"Ayata","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1161\/01.CIR.104.3.304","article-title":"Ubiquitous Elevation of Matrix Metalloproteinase-2 Expression in the Vasculature of Patients with Abdominal Aneurysms","volume":"104","author":"Goodall","year":"2001","journal-title":"Circulation"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1161\/CIRCGENETICS.113.000343","article-title":"Comparison of the Serum Lipidome in Patients with Abdominal Aortic Aneurysm and Peripheral Artery Disease","volume":"7","author":"Moxon","year":"2014","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.ajpath.2012.04.015","article-title":"Fenofibrate Increases High-Density Lipoprotein and Sphingosine 1 Phosphate Concentrations Limiting Abdominal Aortic Aneurysm Progression in a Mouse Model","volume":"181","author":"Krishna","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1124\/mol.104.004317","article-title":"Sphingosine 1-Phosphate Receptors Mediate the Lipid-Induced cAMP Accumulation through Cyclooxygenase-2\/Prostaglandin I2Pathway in Human Coronary Artery Smooth Muscle Cells","volume":"67","author":"Damirin","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"643609","DOI":"10.1155\/2012\/643609","article-title":"Differential Expression of Sphingosine-1-Phosphate Receptors in Abdominal Aortic Aneurysms","volume":"2012","author":"Qu","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0140-6736(20)31179-X","article-title":"Stroke","volume":"396","author":"Campbell","year":"2020","journal-title":"Lancet"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"484","DOI":"10.5603\/PJNNS.a2019.0063","article-title":"Ceramides and sphingosine-1-phosphate as potential markers in diagnosis of ischaemic stroke","volume":"53","author":"Fiedorowicz","year":"2019","journal-title":"Neurol. Neurochir. Polska"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1097\/01.WCB.0000119990.06999.A9","article-title":"Glucosylceramide synthase activity and ceramide levels are modulated during cerebral ischemia after ischemic preconditioning","volume":"24","author":"Takahashi","year":"2004","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"503079","DOI":"10.1155\/2015\/503079","article-title":"Alterations of the Ceramide Metabolism in the Peri-Infarct Cortex Are Independent of the Sphingomyelinase Pathway and Not Influenced by the Acid Sphingomyelinase Inhibitor Fluoxetine","volume":"2015","author":"Brunkhorst","year":"2015","journal-title":"Neural Plast."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.cellsig.2009.11.015","article-title":"Hypoxia-induced neuronal apoptosis is mediated by de novo synthesis of ceramide through activation of serine palmitoyltransferase","volume":"22","author":"Kang","year":"2009","journal-title":"Cell. Signal."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1007\/s12031-022-02014-w","article-title":"Lipidomics Analysis Reveals a Protective Effect of Myriocin on Cerebral Ischemia\/Reperfusion Model Rats","volume":"72","author":"Wang","year":"2022","journal-title":"J. Mol. Neurosci."},{"key":"ref_178","first-page":"1","article-title":"Why there is an Increased Risk of Cardiac Failure, Widening of Pulse Pressure and Hemorrhagic Stroke in Type 2 Diabetics Over Age 60: Roles of Unrecognized Hypomagnesemia and Epigenetics Coupled with Increased Levels of Ceramides, Cytokines, ROS, 4-HNE and Platelet-Activating Factor","volume":"5","author":"Altura","year":"2020","journal-title":"J. Clin. Case Stud."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jfma.2021.01.006","article-title":"Plasma ceramides are associated with outcomes in acute ischemic stroke patients","volume":"121","author":"Lee","year":"2022","journal-title":"J. Formos. Med. Assoc. Taiwan Yi Zhi"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Spijkers, L.J.A., van den Akker, R.F.P., Janssen, B.J.A., Debets, J.J., De Mey, J.G.R., Stroes, E.S.G., van den Born, B.-J.H., Wijesinghe, D.S., Chalfant, C.E., and MacAleese, L. (2011). Hypertension Is Associated with Marked Alterations in Sphingolipid Biology: A Potential Role for Ceramide. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021817"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0168-0102(03)00100-7","article-title":"Neonatal hypoxia\u2013ischemia reduces ganglioside, phospholipid and cholesterol contents in the rat hippocampus","volume":"46","author":"Ramirez","year":"2003","journal-title":"Neurosci. Res."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Whitehead, S.N., Chan, K.H.N., Gangaraju, S., Slinn, J., Li, J., and Hou, S.T. (2011). Imaging mass spectrometry detection of gangliosides species in the mouse brain following transient focal cerebral ischemia and long-term recovery. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020808"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1007\/s12035-018-1317-0","article-title":"Chloroquine Restores Ganglioside Homeostasis and Improves Pathological and Behavioral Outcomes Post-stroke in the Rat","volume":"56","author":"Caughlin","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1179\/016164108X339396","article-title":"L-PDMP improves glucosylceramide synthesis and behavior in rats with focal ischemia","volume":"30","author":"Hisaki","year":"2008","journal-title":"Neurol. Res."},{"key":"ref_185","first-page":"54","article-title":"Monosialotetrahexosy-1 ganglioside attenuates diabetes-associated cerebral ischemia\/reperfusion injury through suppression of the endoplasmic reticulum stress-induced apoptosis","volume":"41","author":"Su","year":"2017","journal-title":"J. Clin. Neurosci. Off. J. Neurosurg. Soc. Australas."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1093\/clinchem\/hvac158","article-title":"Ceramides and Phosphatidylcholines Associate with Cardiovascular Diseases in the Elderly","volume":"68","author":"Koivula","year":"2022","journal-title":"Clin. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jfma.2022.08.021","article-title":"Investigating sphingolipids as biomarkers for the outcomes of acute ischemic stroke patients receiving endovascular treatment","volume":"122","author":"Lee","year":"2023","journal-title":"J. Formos. Med. Assoc. Taiwan Yi Zhi"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Kovilakath, A., Wohlford, G., and Cowart, L.A. (2023). Circulating sphingolipids in heart failure. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1154447"},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Borodzicz-Ja\u017cd\u017cyk, S., Ja\u017cd\u017cyk, P., \u0141ysik, W., Cudnoch-J\u0229drzejewska, A., and Czarzasta, K. (2022). Sphingolipid metabolism and signaling in cardiovascular diseases. Front. Cardiovasc. Med., 9, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9471951\/.","DOI":"10.3389\/fcvm.2022.915961"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1161\/CIRCRESAHA.120.317883","article-title":"Lipid Profiles and Heart Failure Risk: Results From Two Prospective Studies","volume":"128","author":"Wittenbecher","year":"2021","journal-title":"Circ. Res."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"100","DOI":"10.2478\/v10039-011-0057-4","article-title":"Decreased free sphingoid base concentration in the plasma of patients with chronic systolic heart failure","volume":"57","author":"Knapp","year":"2012","journal-title":"Adv. Med. Sci."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"e005708","DOI":"10.1161\/CIRCHEARTFAILURE.118.005708","article-title":"Plasma Ceramides and Sphingomyelins in Relation to Heart Failure Risk","volume":"12","author":"Lemaitre","year":"2019","journal-title":"Circulation. Heart Fail."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1093\/ajh\/hpab105","article-title":"Plasma Ceramides and Cardiovascular Events in Hypertensive Patients at High Cardiovascular Risk","volume":"34","author":"Yin","year":"2021","journal-title":"Am. J. Hypertens."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1016\/j.jacc.2020.02.062","article-title":"Circulating Ceramide 16:0 in Heart Failure with Preserved Ejection Fraction","volume":"75","author":"Javaheri","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"e96203","DOI":"10.1172\/jci.insight.96203","article-title":"Increased de novo ceramide synthesis and accumulation in failing myocardium","volume":"2","author":"Ji","year":"2017","journal-title":"JCI Insight"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1161\/CIRCULATIONAHA.111.060889","article-title":"Ventricular assist device implantation corrects myocardial lipotoxicity, reverses insulin resistance, and normalizes cardiac metabolism in patients with advanced heart failure","volume":"125","author":"Chokshi","year":"2012","journal-title":"Circulation"},{"key":"ref_198","first-page":"565","article-title":"microRNA-21 promotes cardiac fibrosis and development of heart failure with preserved left ventricular ejection fraction by up-regulating Bcl-2","volume":"7","author":"Dong","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1007\/s00125-009-1482-9","article-title":"Link between plasma ceramides, inflammation and insulin resistance: Association with serum IL-6 concentration in patients with coronary heart disease","volume":"52","author":"Lankinen","year":"2009","journal-title":"Diabetologia"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1161\/CIRCULATIONAHA.119.041882","article-title":"Altering Sphingolipid Metabolism Attenuates Cell Death and Inflammatory Response After Myocardial Infarction","volume":"141","author":"Hadas","year":"2020","journal-title":"Circulation"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"H599","DOI":"10.1152\/ajpheart.00314.2021","article-title":"Sphingosine-1-phosphate interactions in the spleen and heart reflect extent of cardiac repair in mice and failing human hearts. American Journal of Physiology","volume":"321","author":"Gowda","year":"2021","journal-title":"Heart Circ. Physiol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s00109-023-02391-8","article-title":"Sphingolipids: Drivers of cardiac fibrosis and atrial fibrillation","volume":"102","author":"Liu","year":"2024","journal-title":"J. Mol. Med."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"e012853","DOI":"10.1161\/JAHA.119.012853","article-title":"Plasma Ceramides and Sphingomyelins in Relation to Atrial Fibrillation Risk: The Cardiovascular Health Study","volume":"9","author":"Jensen","year":"2020","journal-title":"J. Am. Heart Assoc. Cardiovasc. Cerebrovasc. Dis."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s00380-021-01908-w","article-title":"Anti-inflammatory HDL effects are impaired in atrial fibrillation","volume":"37","author":"Holzwirth","year":"2022","journal-title":"Heart Vessel."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1093\/cvr\/cvp312","article-title":"S1P3-mediated cardiac fibrosis in sphingosine kinase 1 transgenic mice involves reactive oxygen species","volume":"85","author":"Takuwa","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1091\/mbc.e09-09-0812","article-title":"Transforming growth factor-beta1 induces transdifferentiation of myoblasts into myofibroblasts via up-regulation of sphingosine kinase-1\/S1P3 axis","volume":"21","author":"Cencetti","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Wilkerson, J.L., Basu, S.K., Stiles, M.A., Prislovsky, A., Grambergs, R.C., Nicholas, S.E., Karamichos, D., Allegood, J.C., Proia, R.L., and Mandal, N. (2022). Ablation of Sphingosine Kinase 1 Protects Cornea from Neovascularization in a Mouse Corneal Injury Model. Cells, 11.","DOI":"10.3390\/cells11182914"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/eurheartj\/ehr269","article-title":"Suppression of persistent atrial fibrillation by genetic knockdown of caspase 3: A pre-clinical pilot study","volume":"34","author":"Trappe","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s10557-009-6199-y","article-title":"Anti-apoptotic effects of a calpain inhibitor on cardiomyocytes in a canine rapid atrial fibrillation model","volume":"23","author":"Li","year":"2009","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1124\/mol.58.2.449","article-title":"Evidence for Edg-3 receptor-mediated activation of I(K.ACh) by sphingosine-1-phosphate in human atrial cardiomyocytes","volume":"58","author":"Himmel","year":"2000","journal-title":"Mol. Pharmacol."},{"key":"ref_211","doi-asserted-by":"crossref","unstructured":"Berkowitz, L., Salazar, C., Ryff, C.D., Coe, C.L., and Rigotti, A. (2022). Serum sphingolipid profiling as a novel biomarker for metabolic syndrome characterization. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.1092331"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.2337\/db06-0330","article-title":"Altered adipose and plasma sphingolipid metabolism in obesity: A potential mechanism for cardiovascular and metabolic risk","volume":"55","author":"Samad","year":"2006","journal-title":"Diabetes"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1007\/s12020-011-9589-4","article-title":"Serum sphingolipids and inflammatory mediators in adolescents at risk for metabolic syndrome","volume":"41","author":"Majumdar","year":"2012","journal-title":"Endocrine"},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Samad, F., Badeanlou, L., Shah, C., and Yang, G. (2011). Adipose tissue and ceramide biosynthesis in the pathogenesis of obesity. Sphingolipids and Metabolic Disease, Springer.","DOI":"10.1007\/978-1-4614-0650-1_5"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nm.2277","article-title":"Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin","volume":"17","author":"Holland","year":"2011","journal-title":"Nat. Med."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"337","DOI":"10.2337\/db08-1228","article-title":"Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance","volume":"58","author":"Haus","year":"2009","journal-title":"Diabetes"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.cmet.2007.01.002","article-title":"Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance","volume":"5","author":"Holland","year":"2007","journal-title":"Cell Metab."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"17426","DOI":"10.1074\/jbc.M112.359950","article-title":"Fenretinide Prevents Lipid-induced Insulin Resistance by Blocking Ceramide Biosynthesis","volume":"287","author":"Bikman","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_219","first-page":"15314","article-title":"Nervonic acid limits weight gain in a mouse model of diet-induced obesity","volume":"34","author":"Keppley","year":"2020","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/hep.26015","article-title":"Ablation of very long acyl chain sphingolipids causes hepatic insulin resistance in mice due to altered detergent-resistant membranes","volume":"57","author":"Park","year":"2013","journal-title":"Hepatology"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1007\/s00125-007-0781-2","article-title":"Increased skeletal muscle ceramide level in men at risk of developing type 2 diabetes","volume":"50","author":"Straczkowski","year":"2007","journal-title":"Diabetologia"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1093\/ajcn\/nqab102","article-title":"The associations between individual plasma SFAs, serine palmitoyl-transferase long-chain base subunit 3 gene rs680379 polymorphism, and type 2 diabetes among Chinese adults","volume":"114","author":"Luo","year":"2021","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1074\/jbc.M103705200","article-title":"Ganglioside GM3 participates in the pathological conditions of insulin resistance","volume":"277","author":"Tagami","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.tem.2015.07.006","article-title":"Ceramides\u2014Lipotoxic Inducers of Metabolic Disorders","volume":"26","author":"Chaurasia","year":"2015","journal-title":"Trends Endocrinol. Metab. TEM"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.cmet.2013.03.019","article-title":"An FGF21-adiponectin-ceramide axis controls energy expenditure and insulin action in mice","volume":"17","author":"Holland","year":"2013","journal-title":"Cell Metab."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.2337\/db06-1619","article-title":"Pharmacological inhibition of glucosylceramide synthase enhances insulin sensitivity","volume":"56","author":"Aerts","year":"2007","journal-title":"Diabetes"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41574-020-0355-7","article-title":"Pancreatic \u03b2-cells in type 1 and type 2 diabetes mellitus: Different pathways to failure","volume":"16","author":"Eizirik","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"20292","DOI":"10.1074\/jbc.M117.814491","article-title":"Overexpression of sphingosine-1-phosphate lyase protects insulin-secreting cells against cytokine toxicity","volume":"292","author":"Hahn","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.cmet.2021.06.006","article-title":"Sphingolipids in Metabolic Disease: The Good, the Bad, and the Unknown","volume":"33","author":"Green","year":"2021","journal-title":"Cell Metab."},{"key":"ref_230","first-page":"743","article-title":"Anti-TCR therapy combined with fingolimod for reversal of diabetic hyperglycemia by \u03b2 cell regeneration in the LEW.1AR1-iddm rat model of type 1 diabetes","volume":"92","author":"Akin","year":"2014","journal-title":"J. Mol. Med."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"4521","DOI":"10.1210\/en.2009-0252","article-title":"Low- and high-density lipoproteins modulate function, apoptosis, and proliferation of primary human and murine pancreatic beta-cells","volume":"150","author":"Ehses","year":"2009","journal-title":"Endocrinology"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1194\/jlr.RA120000875","article-title":"Depletion of adipocyte sphingosine kinase 1 leads to cell hypertrophy, impaired lipolysis, and nonalcoholic fatty liver disease","volume":"61","author":"Anderson","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1210\/en.2015-1768","article-title":"Blockade of Sphingosine 1-Phosphate Receptor 2 Signaling Attenuates High-Fat Diet-Induced Adipocyte Hypertrophy and Systemic Glucose Intolerance in Mice","volume":"157","author":"Kitada","year":"2016","journal-title":"Endocrinology"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1007\/s00125-011-2065-0","article-title":"Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide","volume":"54","author":"Amati","year":"2011","journal-title":"Diabetologia"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1002\/oby.21117","article-title":"Improved insulin sensitivity after exercise training is linked to reduced plasma C14:0 ceramide in obesity and type 2 diabetes","volume":"23","author":"Kasumov","year":"2015","journal-title":"Obesity"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1007\/s11306-019-1596-0","article-title":"Elevated serum ceramides are linked with obesity-associated gut dysbiosis and impaired glucose metabolism","volume":"15","author":"Kayser","year":"2019","journal-title":"Metabolomics: Off. J. Metabolomic Soc."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1111\/j.1872-034X.2011.00815.x","article-title":"Weight loss amelioration of non-alcoholic steatohepatitis linked to shifts in hepatic ceramide expression and serum ceramide levels","volume":"41","author":"Promrat","year":"2011","journal-title":"Hepatol. Res. Off. J. Jpn. Soc. Hepatol."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/ijo.2017.63","article-title":"Serum lipidomics reveals early differential effects of gastric bypass compared with banding on phospholipids and sphingolipids independent of differences in weight loss","volume":"41","author":"Kayser","year":"2017","journal-title":"Int. J. Obes."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s12944-018-0917-z","article-title":"Early postoperative changes of sphingomyelins and ceramides after laparoscopic sleeve gastrectomy","volume":"17","author":"Aslan","year":"2018","journal-title":"Lipids Health Dis."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/oby.22038","article-title":"Bariatric Surgery-Induced Cardiac and Lipidomic Changes in Obesity-Related Heart Failure with Preserved Ejection Fraction","volume":"26","author":"Mikhalkova","year":"2018","journal-title":"Obesity"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1038\/oby.2011.107","article-title":"Gastric bypass surgery reduces plasma ceramide subspecies and improves insulin sensitivity in severely obese patients","volume":"19","author":"Huang","year":"2011","journal-title":"Obesity"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.soard.2011.11.018","article-title":"Reduced cardiovascular risk after bariatric surgery is linked to plasma ceramides, apolipoprotein-B100, and ApoB100\/A1 ratio","volume":"9","author":"Heneghan","year":"2013","journal-title":"Surg. Obes. Relat. Dis. Off. J. Am. Soc. Bariatr. Surg."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/tpj.2013.42","article-title":"Lipidomic profiling before and after Roux-en-Y gastric bypass in obese patients with diabetes","volume":"14","author":"Graessler","year":"2014","journal-title":"Pharmacogenom. J."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.2337\/db15-0809","article-title":"Exercise and Weight Loss Improve Muscle Mitochondrial Respiration, Lipid Partitioning, and Insulin Sensitivity After Gastric Bypass Surgery","volume":"64","author":"Coen","year":"2015","journal-title":"Diabetes"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"16596","DOI":"10.1074\/jbc.M110.186916","article-title":"Differential regulation of dihydroceramide desaturase by palmitate versus monounsaturated fatty acids: Implications for insulin resistance","volume":"286","author":"Hu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.2337\/db12-0363","article-title":"A lipidomics analysis of the relationship between dietary fatty acid composition and insulin sensitivity in young adults","volume":"62","author":"Kien","year":"2013","journal-title":"Diabetes"},{"key":"ref_247","doi-asserted-by":"crossref","unstructured":"Norris, G.H., Milard, M., Michalski, M.-C., and Blesso, C.N. (2019). Protective properties of milk sphingomyelin against dysfunctional lipid metabolism, gut dysbiosis, and inflammation. J. Nutr. Biochem., 73.","DOI":"10.1016\/j.jnutbio.2019.108224"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1093\/jn\/134.10.2611","article-title":"Milk sphingomyelin is more effective than egg sphingomyelin in inhibiting intestinal absorption of cholesterol and fat in rats","volume":"134","author":"Noh","year":"2004","journal-title":"J. Nutr."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/1743-7075-7-90","article-title":"Hepatic accumulation of intestinal cholesterol is decreased and fecal cholesterol excretion is increased in mice fed a high-fat diet supplemented with milk phospholipids","volume":"7","author":"Kamili","year":"2010","journal-title":"Nutr. Metab."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.atherosclerosis.2008.12.004","article-title":"Dietary phospholipid-rich dairy milk extract reduces hepatomegaly, hepatic steatosis and hyperlipidemia in mice fed a high-fat diet","volume":"205","author":"Wat","year":"2009","journal-title":"Atherosclerosis"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jnutbio.2015.12.003","article-title":"Milk sphingomyelin improves lipid metabolism and alters gut microbiota in high fat diet-fed mice","volume":"30","author":"Norris","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"e146161","DOI":"10.1172\/jci.insight.146161","article-title":"Milk polar lipids favorably alter circulating and intestinal ceramide and sphingomyelin species in postmenopausal women","volume":"6","author":"Vors","year":"2021","journal-title":"JCI Insight"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/1476-511X-12-125","article-title":"Effect of dietary sphingomyelin on absorption and fractional synthetic rate of cholesterol and serum lipid profile in humans","volume":"12","author":"Ramprasath","year":"2013","journal-title":"Lipids Health Dis."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"1363077","DOI":"10.3389\/fnut.2024.1363077","article-title":"The impacts of dietary sphingomyelin supplementation on metabolic parameters of healthy adults: A systematic review and meta-analysis of randomized controlled trials","volume":"11","author":"Li","year":"2024","journal-title":"Front. Nutr."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1017\/jns.2016.9","article-title":"Effects of dietary milk- and soya-phospholipids on lipid-parameters and other risk indicators for cardiovascular diseases in overweight or obese men\u2014Two double-blind, randomised, controlled, clinical trials","volume":"5","author":"Weiland","year":"2016","journal-title":"J. Nutr. Sci."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"e1801078","DOI":"10.1002\/mnfr.201801078","article-title":"Milk Polar Lipids in a High-Fat Diet Can Prevent Body Weight Gain: Modulated Abundance of Gut Bacteria in Relation with Fecal Loss of Specific Fatty Acids","volume":"63","author":"Milard","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/mnfr.201500703","article-title":"Dietary emulsifiers from milk and soybean differently impact adiposity and inflammation in association with modulation of colonic goblet cells in high-fat fed mice","volume":"60","author":"Lecomte","year":"2016","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1136\/gutjnl-2018-318155","article-title":"Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: Towards a gut sphingomyelin-cholesterol interplay","volume":"69","author":"Vors","year":"2020","journal-title":"Gut"},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.diabet.2019.06.002","article-title":"Dairy consumption is associated with lower plasma dihydroceramides in women from the D.E.S.I.R. cohort","volume":"46","author":"Fumeron","year":"2020","journal-title":"Diabetes Metab."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.3945\/jn.115.210104","article-title":"Postprandial Plasma Phospholipids in Men Are Influenced by the Source of Dietary Fat","volume":"145","author":"Meikle","year":"2015","journal-title":"J. Nutr."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1017\/S0007114516001264","article-title":"Dairy consumption and CVD: A systematic review and meta-analysis\u2014CORRIGENDUM","volume":"115","author":"Alexander","year":"2016","journal-title":"Br. J. Nutr."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"e002787","DOI":"10.1161\/JAHA.115.002787","article-title":"Dairy Consumption and Risk of Stroke: A Systematic Review and Updated Dose-Response Meta-Analysis of Prospective Cohort Studies","volume":"5","author":"Pan","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1007\/s00394-016-1292-z","article-title":"Cheese consumption and risk of cardiovascular disease: A meta-analysis of prospective studies","volume":"56","author":"Chen","year":"2017","journal-title":"Eur. J. Nutr."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1093\/nutrit\/nuz006","article-title":"Association between dairy intake and the risk of contracting type 2 diabetes and cardiovascular diseases: A systematic review and meta-analysis with subgroup analysis of men versus women","volume":"77","author":"Mishali","year":"2019","journal-title":"Nutr. Rev."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1080\/10408398.2018.1564019","article-title":"Fermented dairy foods intake and risk of cardiovascular diseases: A meta-analysis of cohort studies","volume":"60","author":"Zhang","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1093\/advances\/nmab118","article-title":"Dairy Product Consumption and Cardiovascular Health: A Systematic Review and Meta-analysis of Prospective Cohort Studies","volume":"13","author":"Chen","year":"2022","journal-title":"Adv. Nutr."},{"key":"ref_267","doi-asserted-by":"crossref","unstructured":"Jakobsen, M.U., Trolle, E., Outzen, M., Mejborn, H., Gr\u00f8nberg, M.G., Lyndgaard, C.B., Stockmarr, A., Ven\u00f8, S.K., and Bysted, A. (2021). Intake of dairy products and associations with major atherosclerotic cardiovascular diseases: A systematic review and meta-analysis of cohort studies. Sci. Rep., 11.","DOI":"10.1038\/s41598-020-79708-x"},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1080\/10408398.2017.1392288","article-title":"Food groups and risk of coronary heart disease, stroke and heart failure: A systematic review and dose-response meta-analysis of prospective studies","volume":"59","author":"Bechthold","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s10654-017-0243-1","article-title":"Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality: Dose-response meta-analysis of prospective cohort studies","volume":"32","author":"Guo","year":"2017","journal-title":"Eur. J. Epidemiol."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1007\/s12272-014-0340-6","article-title":"Ginsenoside compound K inhibits angiogenesis via regulation of sphingosine kinase-1 in human umbilical vein endothelial cells","volume":"37","author":"Shin","year":"2014","journal-title":"Arch. Pharmacal. Res."},{"key":"ref_271","doi-asserted-by":"crossref","unstructured":"Meng, Y., Du, Z., Li, Y., Wang, L., Gao, P., Gao, X., Li, C., Zhao, M., Jiang, Y., and Tu, P. (2018). Integration of Metabolomics With Pharmacodynamics to Elucidate the Anti-myocardial Ischemia Effects of Combination of Notoginseng Total Saponins and Safflower Total Flavonoids. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00667"},{"key":"ref_272","doi-asserted-by":"crossref","unstructured":"Wu, F., Lai, S., Fu, D., Liu, J., Wang, C., Feng, H., Liu, J., Li, Z., and Li, P. (2023). Neuroprotective Effects and Metabolomics Study of Protopanaxatriol (PPT) on Cerebral Ischemia\/Reperfusion Injury In Vitro and In Vivo. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021789"},{"key":"ref_273","doi-asserted-by":"crossref","unstructured":"Kwon, Y.-J., Lee, G.-M., Liu, K.-H., and Jung, D.-H. (2021). Effect of Korean Red Ginseng on Plasma Ceramide Levels in Postmenopausal Women with Hypercholesterolemia: A Pilot Randomized Controlled Trial. Metabolites, 11.","DOI":"10.3390\/metabo11070417"},{"key":"ref_274","doi-asserted-by":"crossref","unstructured":"Dai, T., Yan, F., Gong, J., and Liu, S. (2023). Anti-heart failure mechanism of saponin extract of black ginseng based on metabolomics. J. Pharm. Biomed. Anal., 236.","DOI":"10.1016\/j.jpba.2023.115738"},{"key":"ref_275","doi-asserted-by":"crossref","unstructured":"Tian, X., Chen, X., Jiang, Q., Sun, Q., Liu, T., Hong, Y., Zhang, Y., Jiang, Y., Shao, M., and Yang, R. (2022). Notoginsenoside R1 Ameliorates Cardiac Lipotoxicity Through AMPK Signaling Pathway. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.864326"},{"key":"ref_276","doi-asserted-by":"crossref","unstructured":"Tang, M.-M., Zhao, S.-T., Li, R.-Q., and Hou, W. (2023). Therapeutic mechanisms of ginseng in coronary heart disease. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1271029"},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"662","DOI":"10.3945\/jn.115.220459","article-title":"A Healthy Nordic Diet Alters the Plasma Lipidomic Profile in Adults with Features of Metabolic Syndrome in a Multicenter Randomized Dietary Intervention","volume":"146","author":"Lankinen","year":"2015","journal-title":"J. Nutr."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"e13329","DOI":"10.14814\/phy2.13329","article-title":"Efficacy of nutritional interventions to lower circulating ceramides in young adults: FRUVEDomic pilot study","volume":"5","author":"Mathews","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_279","doi-asserted-by":"crossref","unstructured":"Seah, J.Y.H., Chew, W.S., Torta, F., Khoo, C.M., Wenk, M.R., Herr, D.R., Tai, E.S., and van Dam, R.M. (2021). Dietary Fat and Protein Intake in Relation to Plasma Sphingolipids as Determined by a Large-Scale Lipidomic Analysis. Metabolites, 11.","DOI":"10.3390\/metabo11020093"},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.2337\/dc18-0071","article-title":"Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars","volume":"41","author":"Luukkonen","year":"2018","journal-title":"Diabetes Care"},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"6207","DOI":"10.1210\/jc.2019-00160","article-title":"Overeating Saturated Fat Promotes Fatty Liver and Ceramides Compared With Polyunsaturated Fat: A Randomized Trial","volume":"104","author":"Rosqvist","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1172\/JCI43378","article-title":"Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice","volume":"121","author":"Holland","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.abb.2003.08.020","article-title":"Characterizing the effects of saturated fatty acids on insulin signaling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2C12 myotubes","volume":"419","author":"Chavez","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"16090","DOI":"10.1074\/jbc.M807438200","article-title":"Ceramide synthesis is modulated by the sphingosine analog FTY720 via a mixture of uncompetitive and noncompetitive inhibition in an Acyl-CoA chain length-dependent manner","volume":"284","author":"Lahiri","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.bbrc.2010.11.115","article-title":"Gilenya (FTY720) inhibits acid sphingomyelinase by a mechanism similar to tricyclic antidepressants","volume":"404","author":"Dawson","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"18633","DOI":"10.1074\/jbc.M111.220756","article-title":"FTY720 analogues as sphingosine kinase 1 inhibitors: Enzyme inhibition kinetics, allosterism, proteasomal degradation, and actin rearrangement in MCF-7 breast cancer cells","volume":"286","author":"Lim","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/WNF.0b013e3181cbf825","article-title":"Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis","volume":"33","author":"Chun","year":"2010","journal-title":"Clin. Neuropharmacol."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1056\/NEJMoa0907839","article-title":"Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis","volume":"362","author":"Cohen","year":"2010","journal-title":"New Engl. J. Med."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1056\/NEJMoa0909494","article-title":"A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis","volume":"362","author":"Kappos","year":"2010","journal-title":"New Engl. J. Med."},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1161\/CIRCULATIONAHA.106.641407","article-title":"FTY720, a synthetic sphingosine 1 phosphate analogue, inhibits development of atherosclerosis in low-density lipoprotein receptor-deficient mice","volume":"115","author":"Nofer","year":"2007","journal-title":"Circulation"},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1161\/CIRCULATIONAHA.115.012427","article-title":"Sphingosine-1-Phosphate Receptor Agonist Fingolimod Increases Myocardial Salvage and Decreases Adverse Postinfarction Left Ventricular Remodeling in a Porcine Model of Ischemia\/Reperfusion","volume":"133","author":"Vahl","year":"2016","journal-title":"Circulation"},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.yjmcc.2009.10.009","article-title":"FTY720 prevents ischemia\/reperfusion injury-associated arrhythmias in an ex vivo rat heart model via activation of Pak1\/Akt signaling","volume":"48","author":"Egom","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1161\/CIRCULATIONAHA.111.048785","article-title":"Pak1 as a novel therapeutic target for antihypertrophic treatment in the heart","volume":"124","author":"Liu","year":"2011","journal-title":"Circulation"},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1210\/jc.2014-1665","article-title":"Dose-dependent effects of rosuvastatin on the plasma sphingolipidome and phospholipidome in the metabolic syndrome","volume":"99","author":"Ng","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1210\/jc.2013-2559","article-title":"Molecular lipids identify cardiovascular risk and are efficiently lowered by simvastatin and PCSK9 deficiency","volume":"99","author":"Tarasov","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_296","doi-asserted-by":"crossref","unstructured":"Zhao, M., You, B., Wang, X., Huang, J., Zhou, M., Shi, R., and Zhang, G. (2023). Desipramine enhances the stability of atherosclerotic plaque in rabbits monitored with molecular imaging. PLoS ONE, 18, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10062573\/.","DOI":"10.1371\/journal.pone.0283612"},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"2494","DOI":"10.1016\/j.jacc.2021.03.314","article-title":"Fat-Secreted Ceramides Regulate Vascular Redox State and Influence Outcomes in Patients With Cardiovascular Disease","volume":"77","author":"Akawi","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s12933-023-01845-0","article-title":"Liraglutide reduces plasma dihydroceramide levels in patients with type 2 diabetes","volume":"22","author":"Denimal","year":"2023","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"4136","DOI":"10.1210\/jc.2017-00970","article-title":"GLP-1 Receptor Activation Inhibits Palmitate-Induced Apoptosis via Ceramide in Human Cardiac Progenitor Cells","volume":"102","author":"Leonardini","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_300","doi-asserted-by":"crossref","unstructured":"Arag\u00f3n-Herrera, A., Feij\u00f3o-Band\u00edn, S., Santiago, M.O., Barral, L., Campos-Toimil, M., Gil-Longo, J., Pereira, T.M.C., Garc\u00eda-Caballero, T., Rodr\u00edguez-Segade, S., and Rodr\u00edguez, J. (2019). Empagliflozin reduces the levels of CD36 and cardiotoxic lipids while improving autophagy in the hearts of Zucker diabetic fatty rats. Biochem. Pharmacol., 170.","DOI":"10.1016\/j.bcp.2019.113677"},{"key":"ref_301","doi-asserted-by":"crossref","unstructured":"Beckmann, N., Sharma, D., Gulbins, E., Becker, K.A., and Edelmann, B. (2014). Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons. Front. Physiol., 5, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4151525\/.","DOI":"10.3389\/fphys.2014.00331"},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/nm.3214","article-title":"Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs","volume":"19","author":"Gulbins","year":"2013","journal-title":"Nat. Med."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/1749-8090-6-38","article-title":"The challenge to verify ceramide\u2019s role of apoptosis induction in human cardiomyocytes\u2014A pilot study","volume":"6","author":"Usta","year":"2011","journal-title":"J. Cardiothorac. Surg."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"E131","DOI":"10.1152\/ajpendo.00181.2019","article-title":"Amitriptyline inhibits nonalcoholic steatohepatitis and atherosclerosis induced by high-fat diet and LPS through modulation of sphingolipid metabolism","volume":"318","author":"Lu","year":"2020","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/bcpt.13146","article-title":"Tricyclic antidepressant amitriptyline inhibits autophagic flux and prevents tube formation in vascular endothelial cells","volume":"124","author":"Guan","year":"2019","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_306","doi-asserted-by":"crossref","unstructured":"Jiang, M., Huang, S., Duan, W., Liu, Q., and Lei, M. (2019). Inhibition of acid sphingomyelinase activity ameliorates endothelial dysfunction in db\/db mice. Biosci. Rep., 39.","DOI":"10.1042\/BSR20182144"},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.jamcollsurg.2003.12.016","article-title":"Role of ceramide in ischemic preconditioning","volume":"198","author":"Cui","year":"2004","journal-title":"J. Am. Coll. Surg."},{"key":"ref_308","doi-asserted-by":"crossref","unstructured":"Chung, H.-Y., Kollmey, A.S., Schrepper, A., Kohl, M., Bl\u00e4ss, M.F., Stehr, S.N., Lupp, A., Gr\u00e4ler, M.H., and Claus, R.A. (2017). Adjustment of Dysregulated Ceramide Metabolism in a Murine Model of Sepsis-Induced Cardiac Dysfunction. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040839"},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s00395-022-00950-7","article-title":"Acid sphingomyelinase deactivation post-ischemia promotes brain angiogenesis and remodeling by small extracellular vesicles","volume":"117","author":"Yusuf","year":"2022","journal-title":"Basic Res. Cardiol."},{"key":"ref_310","doi-asserted-by":"crossref","unstructured":"Hodun, K., Sztolsztener, K., and Chabowski, A. (2021). Antioxidants Supplementation Reduces Ceramide Synthesis Improving the Cardiac Insulin Transduction Pathway in a Rodent Model of Obesity. Nutrients, 13.","DOI":"10.3390\/nu13103413"},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.yjmcc.2007.06.010","article-title":"Neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats","volume":"43","author":"Adamy","year":"2007","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1161\/01.CIR.0000143630.14515.7C","article-title":"N-acetylcysteine treatment normalizes serum tumor necrosis factor-alpha level and hinders the progression of cardiac injury in hypertensive rats","volume":"110","author":"Bourraindeloup","year":"2004","journal-title":"Circulation"},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"11313","DOI":"10.1074\/jbc.273.18.11313","article-title":"Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-alpha-induced cell death","volume":"273","author":"Liu","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"16281","DOI":"10.1074\/jbc.272.26.16281","article-title":"Inhibition of the neutral magnesium-dependent sphingomyelinase by glutathione","volume":"272","author":"Liu","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"E211","DOI":"10.1152\/ajpendo.91014.2008","article-title":"Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome","volume":"297","author":"Yang","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.2337\/db09-1293","article-title":"Inhibition of de novo ceramide synthesis reverses diet-induced insulin resistance and enhances whole-body oxygen consumption","volume":"59","author":"Ussher","year":"2010","journal-title":"Diabetes"},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"3465","DOI":"10.1161\/01.CIR.0000148370.60535.22","article-title":"Inhibition of sphingomyelin synthesis reduces atherogenesis in apolipoprotein E-knockout mice","volume":"110","author":"Park","year":"2004","journal-title":"Circulation"},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.phrs.2008.06.005","article-title":"Serine palmitoyltransferase inhibitor myriocin induces the regression of atherosclerotic plaques in hyperlipidemic ApoE-deficient mice","volume":"58","author":"Park","year":"2008","journal-title":"Pharmacol. Res."},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/nm.3934","article-title":"Nogo-B regulates endothelial sphingolipid homeostasis to control vascular function and blood pressure","volume":"21","author":"Cantalupo","year":"2015","journal-title":"Nat. Med."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"10284","DOI":"10.1074\/jbc.M412348200","article-title":"Effect of myriocin on plasma sphingolipid metabolism and atherosclerosis in apoE-deficient mice","volume":"280","author":"Hojjati","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1161\/HYPERTENSIONAHA.119.13450","article-title":"Cardiovascular Effects of Pharmacological Targeting of Sphingosine Kinase 1","volume":"75","author":"Nosalski","year":"2020","journal-title":"Hypertension"},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/cvr\/cvw256","article-title":"Sphingosine-1-phosphate signalling-a key player in the pathogenesis of Angiotensin II-induced hypertension","volume":"113","author":"Meissner","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1161\/CIRCULATIONAHA.113.007559","article-title":"Inhibition of glycosphingolipid synthesis ameliorates atherosclerosis and arterial stiffness in apolipoprotein E-\/- mice and rabbits fed a high-fat and -cholesterol diet","volume":"129","author":"Chatterjee","year":"2014","journal-title":"Circulation"},{"key":"ref_324","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.bbrc.2015.07.159","article-title":"Prevention of cardiac hypertrophy by the use of a glycosphingolipid synthesis inhibitor in ApoE-\/- mice","volume":"465","author":"Mishra","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.biomaterials.2015.06.001","article-title":"Improved intervention of atherosclerosis and cardiac hypertrophy through biodegradable polymer-encapsulated delivery of glycosphingolipid inhibitor","volume":"64","author":"Mishra","year":"2015","journal-title":"Biomaterials"},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.bbrc.2020.02.104","article-title":"Management of metabolic syndrome and reduction in body weight in type II diabetic mice by inhibiting glycosphingolipid synthesis","volume":"525","author":"Chatterjee","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_327","doi-asserted-by":"crossref","first-page":"15642","DOI":"10.1074\/jbc.272.25.15642","article-title":"Redox-regulated signaling by lactosylceramide in the proliferation of human aortic smooth muscle cells","volume":"272","author":"Bhunia","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_328","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/nature03711","article-title":"Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes","volume":"436","author":"Yang","year":"2005","journal-title":"Nature"},{"key":"ref_329","doi-asserted-by":"crossref","unstructured":"Thompson, D., Mahmood, S., Morrice, N., Kamli-Salino, S., Dekeryte, R., Hoffmann, P.A., Doherty, M.K., Whitfield, P.D., Delibegovi\u0107, M., and Mody, N. (2023). Fenretinide inhibits obesity and fatty liver disease but induces Smpd3 to increase serum ceramides and worsen atherosclerosis in LDLR\u2212\/\u2212 mice. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-30759-w"},{"key":"ref_330","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1248\/bpb.35.369","article-title":"Fenretinide ameliorates insulin resistance and fatty liver in obese mice","volume":"35","author":"Koh","year":"2012","journal-title":"Biol. Pharm. Bull."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/19\/3296\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:06:12Z","timestamp":1760112372000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/19\/3296"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,28]]},"references-count":330,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["nu16193296"],"URL":"https:\/\/doi.org\/10.3390\/nu16193296","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,28]]}}}