{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:18:41Z","timestamp":1785424721534,"version":"3.56.0"},"reference-count":69,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council of Australia","award":["#1092642"],"award-info":[{"award-number":["#1092642"]}]},{"name":"National Health and Medical Research Council of Australia","award":["#1154749"],"award-info":[{"award-number":["#1154749"]}]},{"award":["#1092642"],"award-info":[{"award-number":["#1092642"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"publisher"}]},{"award":["#1154749"],"award-info":[{"award-number":["#1154749"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In patients with myocardial infarction (MI), the level of sphingolipids, such as ceramide (Cer), is elevated and is associated with an increased risk of progression towards heart failure (HF). Dihydroceramide desaturase 1 (DES1) catalyses the conversion of dihydroceramide (dhCer) into Cer in the de novo sphingolipid pathway. While pharmacological inhibition of DES1 has shown therapeutic benefits in metabolic disease and cancer models, its role in cardiac remodelling remains unclear. This study aimed to determine whether pharmacological inhibition of DES1 using the novel compound, CIN038, attenuates cardiac remodelling following ischemia\u2013reperfusion (I\/R) injury. Three-month-old male C57Bl\/6 mice underwent I\/R or sham surgery (n = 8) and were treated with vehicle or CIN038 (50 mg\/kg\/day, i.p.) for 28 days. Cardiac function, molecular changes, and lipid profiles in circulation and liver were assessed at the endpoint. CIN038 reduced infarct size and cardiac myocyte hypertrophy compared to the I\/R + vehicle group. Profibrotic signalling was reduced in the infarcted hearts, as evidenced by reduced expression of Col1a1, Col3a1, and Tgfb mRNA and decreased levels of \u03b1-SMA and TGF\u03b21 protein expression. Inflammatory signalling was attenuated with reduced ERK and NFkB phosphorylation and suppression of Il-6-STAT axis. Despite these structural and molecular improvements, no changes were observed in cardiac function. Lipidomic analysis revealed selective alterations in circulating and hepatic lipid species, including plasmalogen phosphatidylethanolamines and ether-linked triglycerides, suggesting modulation of lipid metabolism. Collectively, these findings indicate that CIN038 attenuates post-ischemic cardiac remodelling by suppressing inflammatory and profibrotic signalling, highlighting DES1 as a potential therapeutic target following MI.<\/jats:p>","DOI":"10.3390\/ijms27135776","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:55:11Z","timestamp":1782780911000},"page":"5776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Suppression of Post-Ischemic Cardiac Remodelling and Inflammatory Response by a Novel Sphingolipid Modifier, CIN038"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9580-2548","authenticated-orcid":false,"given":"Bing H.","family":"Wang","sequence":"first","affiliation":[{"name":"Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne 3004, Australia"},{"name":"Monash Alfred Baker Centre for Cardiovascular Research, School of Translational Medicine, Monash University, Melbourne 3004, Australia"},{"name":"Biomarker Discovery, Baker Heart and Diabetes Institute, Melbourne 3004, Australia"},{"name":"Centre for Cardiovascular Research in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feby","family":"Savira","sequence":"additional","affiliation":[{"name":"Biomarker Discovery, Baker Heart and Diabetes Institute, Melbourne 3004, Australia"},{"name":"Centre for Cardiovascular Research in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne 3004, Australia"},{"name":"School of Health and Social Development, Faculty of Health, Deakin University, Melbourne 3125, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xiong","sequence":"additional","affiliation":[{"name":"Biomarker Discovery, Baker Heart and 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Group, Baker Heart and Diabetes Institute, Melbourne 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2593-4665","authenticated-orcid":false,"given":"Peter J.","family":"Meikle","sequence":"additional","affiliation":[{"name":"Metabolomics Research Group, Baker Heart and Diabetes Institute, Melbourne 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7497-7082","authenticated-orcid":false,"given":"Darren","family":"Creek","sequence":"additional","affiliation":[{"name":"Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Reid","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Research in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne 3004, Australia"},{"name":"School of 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Melbourne 3004, Australia"},{"name":"Faculty of Medicine, University of Adelaide, Adelaide 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8296-8466","authenticated-orcid":false,"given":"Ruth R.","family":"Magaye","sequence":"additional","affiliation":[{"name":"Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne 3004, Australia"},{"name":"Monash Alfred Baker Centre for Cardiovascular Research, School of Translational Medicine, Monash University, Melbourne 3004, Australia"},{"name":"Biomarker Discovery, Baker Heart and Diabetes Institute, Melbourne 3004, Australia"},{"name":"Centre for Cardiovascular Research in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne 3004, 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Khim."},{"key":"ref_2","first-page":"200","article-title":"Sphingolipids are biomarkers of coronary disease","volume":"17","author":"Lim","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12944-015-0053-y","article-title":"Sphingolipids in cardiovascular diseases and metabolic disorders","volume":"14","author":"Borodzicz","year":"2015","journal-title":"Lipids Health Dis."},{"key":"ref_4","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":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_5","first-page":"40","article-title":"Dihydroceramide desaturase 1, the gatekeeper of ceramide induced lipotoxicity","volume":"1851","author":"Barbarroja","year":"2015","journal-title":"Biochim. Biophys. Acta BBA\u2014Mol. Cell Biol. Lipids"},{"key":"ref_6","first-page":"12","article-title":"Sphingolipid Metabolic Pathway: An Overview of Major Roles Played in Human Diseases","volume":"2013","author":"Vaidyanathan","year":"2013","journal-title":"J. Lipids"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chalfant, C., and De Poeta, M. (2010). An Overview of Sphingolipid Metabolism: From Synthesis to Breakdown. Sphingolipids as Signaling and Regulatory Molecules, Springer.","DOI":"10.1007\/978-1-4419-6741-1"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1172\/JCI131838","article-title":"Machine learning reveals serum sphingolipids as cholesterol-independent biomarkers of coronary artery disease","volume":"130","author":"Poss","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.1016\/j.celrep.2018.08.017","article-title":"Lipidomic Profiles of the Heart and Circulation in Response to Exercise versus Cardiac Pathology: A Resource of Potential Biomarkers and Drug Targets","volume":"24","author":"Tham","year":"2018","journal-title":"Cell Rep."},{"key":"ref_10","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":"Circ. Heart Fail."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e82922","DOI":"10.1172\/jci.insight.82922","article-title":"Increased de novo ceramide synthesis and accumulation in failing myocardium","volume":"2","author":"Ji","year":"2017","journal-title":"JCI Insight"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"340","DOI":"10.2174\/187152012800228661","article-title":"Ceramide and Apoptosis: Exploring the Enigmatic Connections between Sphingolipid Metabolism and Programmed Cell Death","volume":"12","author":"Thomas","year":"2012","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.2741\/4458","article-title":"Implication of sphingosin-1-phosphate in cardiovascular regulation","volume":"21","author":"Li","year":"2016","journal-title":"Front. Biosci. Landmark Ed."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109629","DOI":"10.1016\/j.cellsig.2020.109629","article-title":"Exogenous dihydrosphingosine 1 phosphate mediates collagen synthesis in cardiac fibroblasts through JAK\/STAT signalling and regulation of TIMP1","volume":"72","author":"Magaye","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4167","DOI":"10.18632\/oncotarget.6703","article-title":"Sphingosine kinase 1 is required for TGF-\u03b2 mediated fibroblastto- myofibroblast differentiation in ovarian cancer","volume":"7","author":"Beach","year":"2016","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, E., He, X., and Zeng, M. (2019). The Role of S1P and the Related Signaling Pathway in the Development of Tissue Fibrosis. Front. Pharmacol., 9, Erratum in Front. Pharmacol. 2020, 11, 594471.","DOI":"10.3389\/fphar.2020.594471"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2045894018816977","DOI":"10.1177\/2045894018816977","article-title":"SphK1\/S1P mediates TGF-\u03b21-induced proliferation of pulmonary artery smooth muscle cells and its potential mechanisms","volume":"9","author":"Wang","year":"2019","journal-title":"Pulm. Circ."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"24754","DOI":"10.1074\/jbc.M111.250779","article-title":"Identification of Dihydroceramide Desaturase as a Direct in Vitro Target for Fenretinide","volume":"286","author":"Rahmaniyan","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1126\/science.aav3722","article-title":"Targeting a ceramide double bond improves insulin resistance and hepatic steatosis","volume":"365","author":"Chaurasia","year":"2019","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.chemphyslip.2015.07.025","article-title":"Inhibitors of dihydroceramide desaturase 1: Therapeutic agents and pharmacological tools to decipher the role of dihydroceramides in cell biology","volume":"197","author":"Casasampere","year":"2016","journal-title":"Chem. Phys. Lipids"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41419-019-1775-y","article-title":"A new bioavailable fenretinide formulation with antiproliferative, antimetabolic, and cytotoxic effects on solid tumors","volume":"10","author":"Orienti","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.2337\/db14-0359","article-title":"Increased dihydroceramide\/ceramide ratio mediated by defective expression of degs1 impairs adipocyte differentiation and function","volume":"64","author":"Barbarroja","year":"2015","journal-title":"Diabetes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1146\/annurev-physiol-031620-093815","article-title":"Ceramides in Metabolism: Key Lipotoxic Players","volume":"83","author":"Chaurasia","year":"2021","journal-title":"Annu. Rev. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5110","DOI":"10.1074\/jbc.M116.751602","article-title":"Novel Interconnections in Lipid Metabolism Revealed by Overexpression of Sphingomyelin Synthase-1*","volume":"292","author":"Deevska","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_26","first-page":"1","article-title":"Hepatic triglyceride accumulation via endoplasmic reticulum stress-induced SREBP-1 activation is regulated by ceramide synthases","volume":"51","author":"Kim","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1021\/acs.jmedchem.5b01439","article-title":"From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure\u2013Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II)","volume":"59","author":"Aurelio","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100222","DOI":"10.1016\/j.jlr.2022.100222","article-title":"Adaptations of the 3T3-L1 adipocyte lipidome to defective ether lipid catabolism upon Agmo knockdown","volume":"63","author":"Sailer","year":"2022","journal-title":"J. Lipid Res."},{"key":"ref_29","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_30","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 BBA\u2014Gen. Subj."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Siddique, M.M., Bikman, B.T., Wang, L., Ying, L., Reinhardt, E., Shui, G., Wenk, M.R., and Summers, S.A. (2012). Ablation of Dihydroceramide Desaturase Confers Resistance to Etoposide-Induced Apoptosis In Vitro. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044042"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41420-018-0075-0","article-title":"Targeting sphingolipid metabolism as an approach for combination therapies in haematological malignancies","volume":"4","author":"Lewis","year":"2018","journal-title":"Cell Death Discov."},{"key":"ref_33","first-page":"62","article-title":"Cardiac Remodeling: Concepts, Clinical Impact, Pathophysiological Mechanisms and Pharmacologic Treatment","volume":"106","author":"Azevedo","year":"2016","journal-title":"Arq. Bras. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0735-1097(99)00630-0","article-title":"Cardiac remodeling\u2014Concepts and clinical implications: A consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling","volume":"35","author":"Cohn","year":"2000","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s10554-015-0657-3","article-title":"The impact of infarct size on regional and global left ventricular systolic function: A cardiac magnetic resonance imaging study","volume":"31","author":"Palazzuoli","year":"2015","journal-title":"Int. J. Cardiovasc. Imaging"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"D\u00f6rmann, N., Hammer, E., Struckmann, K., R\u00fcdebusch, J., Bartels, K., Wenzel, K., Schulz, J., Gross, S., Schwanz, S., and Martin, E. (2024). Metabolic remodeling in cardiac hypertrophy and heart failure with reduced ejection fraction occurs independent of transcription factor EB in mice. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1323760"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1002\/ejhf.3264","article-title":"Mechanisms of myocardial reverse remodelling and its clinical significance: A scientific statement of the ESC Working Group on Myocardial Function","volume":"26","author":"Ferreira","year":"2024","journal-title":"Eur. J. Heart Fail."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"118628","DOI":"10.1016\/j.lfs.2020.118628","article-title":"Cardioprotection of pharmacological postconditioning on myocardial ischemia\/reperfusion injury","volume":"264","author":"Wu","year":"2021","journal-title":"Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrneph.2016.48","article-title":"TGF-[beta]: The master regulator of fibrosis","volume":"12","author":"Meng","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1021\/acs.jproteome.1c00098","article-title":"Myocardial Infarction Induces Cardiac Fibroblast Transformation within Injured and Noninjured Regions of the Mouse Heart","volume":"20","author":"Shah","year":"2021","journal-title":"J. Proteome Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.toxlet.2021.07.012","article-title":"Sphingolipid imbalance and inflammatory effects induced by uremic toxins in heart and kidney cells are reversed by dihydroceramide desaturase 1 inhibition","volume":"350","author":"Savira","year":"2021","journal-title":"Toxicol. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"106923","DOI":"10.1016\/j.vph.2021.106923","article-title":"The effect of dihydroceramide desaturase 1 inhibition on endothelial impairment induced by indoxyl sulfate","volume":"141","author":"Savira","year":"2021","journal-title":"Vasc. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"a022129","DOI":"10.1101\/cshperspect.a022129","article-title":"Non-Smad Signaling Pathways of the TGF-\u03b2 Family","volume":"9","author":"Zhang","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"21364","DOI":"10.1038\/s41598-020-78206-4","article-title":"Canonical and noncanonical TGF-\u03b2 signaling regulate fibrous tissue differentiation in the axial skeleton","volume":"10","author":"Clayton","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"116413","DOI":"10.1016\/j.biopha.2024.116413","article-title":"Targeting MAPK-ERK\/JNK pathway: A potential intervention mechanism of myocardial fibrosis in heart failure","volume":"173","author":"Zhang","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kurdi, M., Zgheib, C., and Booz, G.W. (2018). Recent Developments on the Crosstalk Between STAT3 and Inflammation in Heart Function and Disease. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.03029"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2353\/ajpath.2007.061078","article-title":"Classic interleukin-6 receptor signaling and interleukin-6 trans-signaling differentially control angiotensin II-dependent hypertension, cardiac signal transducer and activator of transcription-3 activation, and vascular hypertrophy in vivo","volume":"171","author":"Coles","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Harhous, Z., Booz, G.W., Ovize, M., Bidaux, G., and Kurdi, M. (2019). An Update on the Multifaceted Roles of STAT3 in the Heart. Front. Cardiovasc. Med., 6.","DOI":"10.3389\/fcvm.2019.00150"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1038\/s41467-026-69196-4","article-title":"Tissue-resident macrophage survival depends on mitochondrial function regulated by SerpinB2 in chronic inflammation","volume":"17","author":"Vasamsetti","year":"2026","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1002\/1873-3468.14973","article-title":"Sphingosine-1-phosphate signalling in the heart: Exploring emerging perspectives in cardiopathology","volume":"598","author":"Phan","year":"2024","journal-title":"FEBS Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"H250","DOI":"10.1152\/ajpheart.00372.2015","article-title":"Sphingosine 1-phosphate signaling contributes to cardiac inflammation, dysfunction, and remodeling following myocardial infarction","volume":"310","author":"Zhang","year":"2016","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1007\/s00018-018-2765-4","article-title":"Lipids in the cell: Organisation regulates function","volume":"75","author":"Santos","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"14764","DOI":"10.1038\/s41598-018-33116-4","article-title":"Cholesterol is Inefficiently Converted to Cholesteryl Esters in the Blood of Cardiovascular Disease Patients","volume":"8","author":"Gerl","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Maxfield, F.R., Steinfeld, N., and Ma, C.J. (2023). The formation and consequences of cholesterol-rich deposits in atherosclerotic lesions. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1148304"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Bozelli, J.C., Azher, S., and Epand, R.M. (2021). Plasmalogens and Chronic Inflammatory Diseases. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.730829"},{"key":"ref_57","first-page":"e4265","article-title":"Lipid Profile of Patients with Acute Myocardial Infarction (AMI)","volume":"11","author":"Kumar","year":"2019","journal-title":"Cureus"},{"key":"ref_58","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_59","first-page":"CR490","article-title":"Plasma sphingosine-1-phosphate concentration is reduced in patients with myocardial infarction","volume":"15","author":"Knapp","year":"2009","journal-title":"Med. Sci. Monit."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"101309","DOI":"10.1016\/j.jacbts.2025.05.004","article-title":"The Cardiohepatic Axis in Metabolic Disease: Liver to Heart","volume":"10","author":"Hakeem","year":"2025","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"100092","DOI":"10.1016\/j.jlr.2021.100092","article-title":"Shark liver oil supplementation enriches endogenous plasmalogens and reduces markers of dyslipidemia and inflammation","volume":"62","author":"Paul","year":"2021","journal-title":"J. Lipid Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ijcard.2009.01.019","article-title":"Infarct size and post-infarct inflammation determine the risk of cardiac rupture in mice","volume":"143","author":"Gao","year":"2010","journal-title":"Int. J. Cardiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.cardiores.2004.10.014","article-title":"Mouse model of post-infarct ventricular rupture: Time course, strain- and gender-dependency, tensile strength, and histopathology","volume":"65","author":"Gao","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1161\/01.CIR.101.1.71","article-title":"\u03b22-Adrenergic Receptor Overexpression Exacerbates Development of Heart Failure After Aortic Stenosis","volume":"101","author":"Du","year":"2000","journal-title":"Circulation"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.chembiol.2018.10.008","article-title":"High-Throughput Plasma Lipidomics: Detailed Mapping of the Associations with Cardiometabolic Risk Factors","volume":"26","author":"Huynh","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1016\/j.ijcard.2012.12.065","article-title":"Subtotal nephrectomy accelerates pathological cardiac remodeling post-myocardial infarction: Implications for cardiorenal syndrome","volume":"168","author":"Liu","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"105952","DOI":"10.1016\/j.biocel.2021.105952","article-title":"Attenuating PI3K\/Akt- mTOR pathway reduces dihydrosphingosine 1 phosphate mediated collagen synthesis and hypertrophy in primary cardiac cells","volume":"134","author":"Magaye","year":"2021","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1093\/eurheartj\/ehp574","article-title":"Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts and myocytes?","volume":"31","author":"Lekawanvijit","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1161\/01.RES.56.6.884","article-title":"Stimulation of hypertrophy of cultured neonatal rat heart cells through an alpha 1-adrenergic receptor and induction of beating through an alpha 1- and beta 1-adrenergic receptor interaction. Evidence for independent regulation of growth and beating","volume":"56","author":"Simpson","year":"1985","journal-title":"Circ. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5776\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:58:49Z","timestamp":1782781129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,26]]},"references-count":69,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135776"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135776","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,26]]}}}