{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:45:42Z","timestamp":1782877542149,"version":"3.54.5"},"reference-count":105,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T00:00:00Z","timestamp":1776470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Phospholipid transfer protein (PLTP) is a lipid transfer protein classically studied in the context of plasma lipoprotein metabolism, high-density lipoprotein (HDL) remodeling, and cardiovascular disease risk. PLTP facilitates phospholipid transfer between lipoproteins and regulates HDL particle size and composition through interactions with apolipoprotein A-I and apolipoprotein A-II. While its systemic roles in cholesterol handling, reverse cholesterol transport, and inflammatory signaling are well established, the cell-autonomous functions of PLTP within cardiomyocytes remain poorly defined, particularly in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Extensive experimental and clinical studies demonstrate that PLTP enhances ABCA1-dependent cholesterol efflux primarily by stabilizing ABCA1 at the plasma membrane and by promoting the generation of lipid-poor apolipoprotein A-I and pre-\u03b2 HDL particles, which serve as efficient cholesterol acceptors; the magnitude of these effects depends on cellular context, PLTP expression levels, and the availability of lipid acceptors. PLTP expression is metabolically regulated and widely distributed across tissues, including macrophages and other non-hepatic cells, supporting roles beyond circulating lipoprotein remodeling. Altered PLTP activity has been linked to atherosclerosis, cardiovascular disease, and inflammatory pathways, underscoring its relevance to cardiac pathophysiology. Emerging evidence further suggests that intracellular cholesterol distribution, rather than total cholesterol content alone, critically influences mitochondrial membrane composition, bioenergetics, and stress signaling in cardiomyocytes. These observations raise the possibility that PLTP-regulated lipid flux may indirectly shape mitochondrial function by modulating cellular cholesterol homeostasis. This review synthesizes current knowledge of PLTP biology, cholesterol metabolism, and lipoprotein remodeling, and integrates these concepts with emerging frameworks in cardiomyocyte lipid metabolism and mitochondrial physiology. We highlight human iPSC-derived cardiomyocytes as a strategic and translationally relevant platform to investigate PLTP\u2019s non-canonical, cell-intrinsic roles, identify critical knowledge gaps, and propose future directions for elucidating how PLTP may influence mitochondrial function in human cardiac cells.<\/jats:p>","DOI":"10.3390\/ijms27083617","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:24:23Z","timestamp":1776673463000},"page":"3617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Phospholipid Transfer Protein (PLTP) in Cholesterol Handling: Implications for Mitochondrial Lipid Homeostasis in Human iPSC-Derived Cardiomyocytes"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3642-6035","authenticated-orcid":false,"given":"Dhienda C.","family":"Shahannaz","sequence":"first","affiliation":[{"name":"Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4698-9814","authenticated-orcid":false,"given":"Tadahisa","family":"Sugiura","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1093\/cvr\/cvad041","article-title":"Cardiomyocyte-specific PCSK9 deficiency compromises mitochondrial bioenergetics and heart function","volume":"119","author":"Laudette","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1161\/CIRCRESAHA.125.326464","article-title":"Impact of cholesterol on cardiac mitochondrial function","volume":"136","author":"Lopaschuk","year":"2025","journal-title":"Circ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lupu, D., Sc\u00e2rneciu, C.C., \u021a\u00een\u021b, D., and Tudoran, C. (2025). Cirrhotic Cardiomyopathy: Bridging hepatic and cardiac pathophysiology in the modern era. J. Clin. Med., 14.","DOI":"10.3390\/jcm14175993"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nikouee, A., Uchida, K., Moench, I., and Lopatin, A.N. (2018). Cholesterol protects against acute Stress-Induced T-Tubule remodeling in mouse ventricular myocytes. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01516"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1161\/CIRCRESAHA.124.325629","article-title":"PCSK9 regulates cardiac mitochondrial cholesterol by promoting TSPO degradation","volume":"136","author":"Laudette","year":"2025","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102643","DOI":"10.1016\/j.redox.2023.102643","article-title":"Mitochondrial cholesterol: Metabolism and impact on redox biology and disease","volume":"61","author":"Goicoechea","year":"2023","journal-title":"Redox Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"jcs263907","DOI":"10.1242\/jcs.263907","article-title":"A lipid in transit\u2014The journey of cholesterol into the heart of mitochondrial research","volume":"138","author":"Simmen","year":"2025","journal-title":"J. Cell Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1016\/j.freeradbiomed.2015.08.010","article-title":"Mitochondrial regulation of macrophage cholesterol homeostasis","volume":"89","author":"Graham","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Baumblatt, J., Carroll, M., Fryar, C., Baumblatt, J., and Iniguez, M. (2024). Total and High-Density lipoprotein cholesterol in Adults: United States, August 2021\u2013August 2023. Cent. Dis. Control. (CDC).","DOI":"10.15620\/cdc\/165796"},{"key":"ref_10","unstructured":"American Heart Association, Inc. (2026). 2026 Heart Disease & Stroke Statistics Update Fact Sheet, American Heart Association, Inc.. Available online: https:\/\/professional.heart.org\/en\/-\/media\/PHD-Files-2\/Science-News\/2\/2026-Heart-and-Stroke-Stat-Update\/Translations\/English\/2026-Stats-Update-Fact-Sheet-US-Sex-and-Race-and-CVD_final.pdf?sc_lang=en."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"979","DOI":"10.2147\/VHRM.S5685","article-title":"Low high-density lipoprotein cholesterol: Current status and future strategies for management","volume":"6","author":"Singh","year":"2010","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1161\/CIRCRESAHA.119.312617","article-title":"HDL and Reverse Cholesterol Transport","volume":"124","author":"Ouimet","year":"2019","journal-title":"Circ. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3803\/EnM.2017.32.1.41","article-title":"The role of macrophage lipophagy in reverse cholesterol transport","volume":"32","author":"Jeong","year":"2017","journal-title":"Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1016\/j.cmet.2024.07.024","article-title":"Mitochondrial membrane lipids in the regulation of bioenergetic flux","volume":"36","author":"Decker","year":"2024","journal-title":"Cell Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ceb.2020.01.006","article-title":"Reign in the membrane: How common lipids govern mitochondrial function","volume":"63","author":"Funai","year":"2020","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1093\/cvr\/cvad100","article-title":"Cardiac lipid metabolism, mitochondrial function, and heart failure","volume":"119","author":"Cabodevilla","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1194\/jlr.R082503","article-title":"Phospholipid transfer protein: Its impact on lipoprotein homeostasis and atherosclerosis","volume":"59","author":"Jiang","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"429","DOI":"10.17219\/acem\/67968","article-title":"Plasma lipid transfer proteins: The role of PLTP and CETP in atherogenesis","volume":"27","author":"Chowaniec","year":"2018","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nri3793","article-title":"Cholesterol, inflammation and innate immunity","volume":"15","author":"Tall","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e143526","DOI":"10.1172\/jci.insight.143526","article-title":"Metabolism of PLTP, CETP, and LCAT on multiple HDL sizes using the Orbitrap Fusion Lumos","volume":"6","author":"Singh","year":"2021","journal-title":"JCI Insight"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Xu, Z., Yang, S., and Cui, L. (2024). Understanding the heterogeneity and dysfunction of HDL in chronic kidney disease: Insights from recent reviews. BMC Nephrol., 25.","DOI":"10.1186\/s12882-024-03808-3"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-981-15-6082-8_1","article-title":"Impact of Phospholipid Transfer Protein in Lipid Metabolism and Cardiovascular Diseases","volume":"1276","author":"Jiang","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/S0140-6736(14)61217-4","article-title":"HDL and cardiovascular disease","volume":"384","author":"Rader","year":"2014","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nrcardio.2015.124","article-title":"Dysfunctional HDL and atherosclerotic cardiovascular disease","volume":"13","author":"Rosenson","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hajny, S., and Christoffersen, C. (2017). A novel perspective on the APOM-S1P axis, highlighting the metabolism of APOM and its role in liver fibrosis and neuroinflammation. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081636"},{"key":"ref_26","first-page":"4","article-title":"Features of cholesterol metabolism in macrophages in immunoinflammatory diseases","volume":"7","author":"Bogatyreva","year":"2023","journal-title":"Vessel. Plus"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1152\/physrev.00005.2005","article-title":"ATP-Binding Cassette Transporter A1: A cell cholesterol exporter that protects against cardiovascular disease","volume":"85","author":"Oram","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"24020","DOI":"10.1074\/jbc.R114.583658","article-title":"Molecular mechanisms of Cellular Cholesterol Efflux","volume":"289","author":"Phillips","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e49828","DOI":"10.15252\/embr.201949828","article-title":"The regulation of glucose and lipid homeostasis via PLTP as a mediator of BAT-liver communication","volume":"21","author":"Sponton","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3090","DOI":"10.1172\/JCI30163","article-title":"Molecular regulation of HDL metabolism and function: Implications for novel therapies","volume":"116","author":"Rader","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1172\/JCI114718","article-title":"Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery","volume":"86","author":"Simon","year":"1990","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1161\/01.ATV.0000089080.76134.CE","article-title":"Phospholipid transfer protein and atherosclerosis","volume":"23","author":"Tall","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1124\/pr.58.3.1","article-title":"Functionally defective High-Density lipoprotein: A new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis","volume":"58","author":"Kontush","year":"2006","journal-title":"Pharmacol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1161\/ATVBAHA.114.303764","article-title":"Adipocyte phospholipid transfer protein and lipoprotein metabolism","volume":"35","author":"Jiang","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1161\/01.ATV.0000094433.98445.7F","article-title":"High plasma phospholipid transfer protein levels as a risk factor for coronary artery disease","volume":"23","author":"Schlitt","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1161\/ATVBAHA.107.149914","article-title":"Phospholipid transfer Protein\u2013Deficient mice absorb less cholesterol","volume":"27","author":"Liu","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1161\/CIRCRESAHA.123.321563","article-title":"HDL function and atherosclerosis: Reactive dicarbonyls as promising targets of therapy","volume":"132","author":"Linton","year":"2023","journal-title":"Circ. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S201","DOI":"10.1194\/jlr.R800061-JLR200","article-title":"The role of plasma lipid transfer proteins in lipoprotein metabolism and atherogenesis","volume":"50","author":"Masson","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Lebrun, L.J., Pallot, G., Nguyen, M., Tavernier, A., Dusuel, A., Pilot, T., Deckert, V., Dugail, I., Le Guern, N., and De Barros, J.-P.P. (2022). Increased weight gain and insulin resistance in HF-Fed PLTP deficient mice is related to altered inflammatory response and plasma transport of Gut-Derived LPS. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113226"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/s41423-018-0036-9","article-title":"Plasma phospholipid transfer protein (PLTP) as an emerging determinant of the adaptive immune response","volume":"15","author":"Desrumaux","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sugiura, T., Shahannaz, D.C., and Ferrell, B.E. (2024). Current status of cardiac regenerative therapy using induced pluripotent stem cells. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202404.1796.v1"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Shahannaz, D.C., Sugiura, T., Ferrell, B.E., and Yoshida, T. (2025). Targeting mitochondrial dynamics via EV delivery in regenerative cardiology: Mechanistic and therapeutic perspectives. Cells, 14.","DOI":"10.3390\/cells14211738"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Shahannaz, D.C., Sugiura, T., and Yoshida, T. (2025). Mitochondria-Enriched Extracellular Vesicles (EVs) for Cardiac Bioenergetics Restoration: A Scoping Review of Preclinical Mechanisms and Source-Specific Strategies. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262211052"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.36922\/gtm.5745","article-title":"Advancements in cardiac regenerative therapy: Scalable human iPSC-derived cardiomyocyte differentiation and maturation","volume":"4","author":"Sugiura","year":"2025","journal-title":"Glob. Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"20240915","DOI":"10.1515\/med-2024-0915","article-title":"Phospholipid transfer protein ameliorates sepsis-induced cardiac dysfunction through NLRP3 inflammasome inhibition","volume":"19","author":"Wang","year":"2024","journal-title":"Open Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Shahannaz, D.C., Sugiura, T., and Ferrell, B.E. (2025). Enhancing mitochondrial maturation in IPSC-DerivedCardiomyocytes: Strategies for Metabolic Optimization. BioChem, 5.","DOI":"10.3390\/biochem5030023"},{"key":"ref_47","first-page":"22","article-title":"From injury to repair: The therapeutic potential of induced pluripotent stem cells in heart failure","volume":"2","author":"Sugiura","year":"2025","journal-title":"Regen. Med. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4","DOI":"10.36922\/JCTR025230026","article-title":"The role of large language models in induced pluripotent stem cell-derived cardiomyocytes research and clinical translation","volume":"11","author":"Shahannaz","year":"2025","journal-title":"J. Clin. Transl. Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Shahannaz, D.C., Sugiura, T., Ferrell, B.E., and Yoshida, T. (2025). Arrhythmogenic Risk in IPSC-Derived Cardiomyocytes: Current limitations and therapeutic Perspectives. Medicina, 61.","DOI":"10.3390\/medicina61112056"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Shahannaz, D.C., Sugiura, T., Ferrell, B.E., and Yoshida, T. (2026). Engineering Mitochondrial Biogenesis in iPSC-CMs: CRISPR-Guided Approaches for Advanced Cardiomyocyte Development. J. Cardiovasc. Dev. Dis., 13.","DOI":"10.3390\/jcdd13020077"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Shahannaz, D.C., and Sugiura, T. (2026). EV-Encapsulated Mitochondrial miRNAs: Enhancing Cardiomyocyte Bioenergetics. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27052224"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.plipres.2013.07.002","article-title":"Lipids of mitochondria","volume":"52","author":"Horvath","year":"2013","journal-title":"Prog. Lipid Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Shahannaz, D.C., and Sugiura, T. (2026). Engineering Smart Biomaterial Interfaces for iPSC-CM Maturation: A Biophysical and Metabolic Reprogramming Approach to Regenerative Cardiac Medicine. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27062637"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"21896","DOI":"10.1073\/pnas.2004807117","article-title":"How cholesterol stiffens unsaturated lipid membranes","volume":"117","author":"Chakraborty","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","first-page":"22","article-title":"Next-Generation Metabolic Reprogramming in iPSC-Derived Cardiomyocytes: CRISPR-EV Synergy for Precision Cardiac Regeneration","volume":"2","author":"Shahannaz","year":"2026","journal-title":"Biomedicines"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Giraldo-Lorza, J.M., Leidy, C., and Manrique-Moreno, M. (2024). The influence of cholesterol on membrane targeted bioactive peptides: Modulating peptide activity through changes in bilayer biophysical properties. Membranes, 14.","DOI":"10.3390\/membranes14100220"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.atherosclerosis.2013.01.046","article-title":"Plasma lipid transfer proteins and cardiovascular disease. The Framingham Heart Study","volume":"228","author":"Robins","year":"2013","journal-title":"Atherosclerosis"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1161\/CIRCULATIONAHA.109.912519","article-title":"Genetic variation at the phospholipid transfer protein locus affects its activity and high-density lipoprotein size and is a novel marker of cardiovascular disease susceptibility","volume":"122","author":"Vergeer","year":"2010","journal-title":"Circulation"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5388","DOI":"10.1093\/hmg\/ddv262","article-title":"Phospholipid transfer protein (PLTP) deficiency accelerates memory dysfunction through altering amyloid precursor protein (APP) processing in a mouse model of Alzheimer\u2019s disease","volume":"24","author":"Tong","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_60","first-page":"90","article-title":"Mitochondrial cholesterol import","volume":"1862","author":"Elustondo","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"101214","DOI":"10.1016\/j.redox.2019.101214","article-title":"Cholesterol enrichment in liver mitochondria impairs oxidative phosphorylation and disrupts the assembly of respiratory supercomplexes","volume":"24","author":"Fucho","year":"2019","journal-title":"Redox Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"52873","DOI":"10.1074\/jbc.M308366200","article-title":"Cardiolipin stabilizes respiratory chain supercomplexes","volume":"278","author":"Pfeiffer","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Montesinos, J., Kabra, K., Uceda, M., Larrea, D., Agrawal, R.R., Tamucci, K.A., Pera, M., Ferre, A.C., Gomez-Lopez, N., and Yun, T.D. (2024). The contribution of mitochondria-associated ER membranes to cholesterol homeostasis. bioRxiv, bioRxiv:2024.11.11.622945.","DOI":"10.1101\/2024.11.11.622945"},{"key":"ref_64","first-page":"484","article-title":"Bax activation and stress-induced apoptosis delayed by the accumulation of cholesterol in mitochondrial membranes","volume":"15","author":"Montessuit","year":"2007","journal-title":"Cell Death Differ."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.bbrc.2011.12.022","article-title":"The role of cholesterol in the association of endoplasmic reticulum membranes with mitochondria","volume":"417","author":"Fujimoto","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_66","first-page":"117","article-title":"Mitochondrial cholesterol in health and disease","volume":"24","author":"Mari","year":"2009","journal-title":"Histol. Histopathol."},{"key":"ref_67","first-page":"636","article-title":"Intracellular sterol dynamics","volume":"1791","author":"Mesmin","year":"2009","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/s41580-019-0190-7","article-title":"Mechanisms and regulation of cholesterol homeostasis","volume":"21","author":"Luo","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Griffiths, W.J., and Wang, Y. (2021). Sterols, oxysterols, and accessible cholesterol: Signalling for homeostasis, in immunity and during development. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.723224"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ceb.2015.04.002","article-title":"Novel mechanisms of intracellular cholesterol transport: Oxysterol-binding proteins and membrane contact sites","volume":"35","author":"Du","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1096\/fj.201601309","article-title":"On the Pathogenesis of Alzheimer\u2019s Disease: The MAM Hypothesis","volume":"31","author":"Schon","year":"2017","journal-title":"FASEB J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1089\/ars.2013.5280","article-title":"Cardiolipin and mitochondrial function in health and disease","volume":"20","author":"Paradies","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_73","first-page":"a041404","article-title":"Intracellular Cholesterol Trafficking. Cold Spring Harb","volume":"15","author":"Ikonen","year":"2023","journal-title":"Perspect Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.bcp.2017.06.125","article-title":"A TSPO ligand prevents mitochondrial sterol accumulation and dysfunction during myocardial ischemia-reperfusion in hypercholesterolemic rats","volume":"142","author":"Musman","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s00395-023-01025-x","article-title":"Statins affect human iPSC-derived cardiomyocytes by interfering with mitochondrial function and intracellular acidification","volume":"119","author":"Somers","year":"2024","journal-title":"Basic Res. Cardiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.bbabio.2010.02.010","article-title":"Cholesterol and peroxidized cardiolipin in mitochondrial membrane properties, permeabilization and cell death","volume":"1797","author":"Montero","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e12076","DOI":"10.1002\/jev2.12076","article-title":"Engineered extracellular vesicles as versatile ribonucleoprotein delivery vehicles for efficient and safe CRISPR genome editing","volume":"10","author":"Yao","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.jconrel.2024.05.023","article-title":"Small extracellular vesicle-mediated CRISPR-Cas9 RNP delivery for cardiac-specific genome editing","volume":"370","author":"Mun","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Zhu, X., Gao, M., Yang, Y., Li, W., Bao, J., and Li, Y. (2023). The CRISPR\/Cas9 System Delivered by Extracellular Vesicles. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15030984"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1093\/cvr\/cvaa125","article-title":"Human-induced pluripotent stem cells for modelling metabolic perturbations and impaired bioenergetics underlying cardiomyopathies","volume":"117","author":"Ramachandra","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"107925","DOI":"10.1016\/j.celrep.2020.107925","article-title":"Metabolic Maturation Media Improve Physiological Function of Human iPSC-Derived Cardiomyocytes","volume":"32","author":"Feyen","year":"2020","journal-title":"Cell Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/scrt380","article-title":"Induced pluripotent stem cell-derived cardiomyocytes for cardiovascular disease modeling and drug screening","volume":"4","author":"Sharma","year":"2013","journal-title":"Stem Cell Res. Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nrg.2018.4","article-title":"Integrative omics for health and disease","volume":"19","author":"Karczewski","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_84","first-page":"e000043","article-title":"Induced Pluripotent Stem Cells for Cardiovascular Disease Modeling and Precision Medicine: A Scientific Statement from the American Heart Association","volume":"11","author":"Musunuru","year":"2018","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"281","DOI":"10.4252\/wjsc.v13.i4.281","article-title":"Patient-specific induced pluripotent stem cells as \u201cdisease-in-a-dish\u201d models for inherited cardiomyopathies and channelopathies\u201415 years of research","volume":"13","author":"Micheu","year":"2021","journal-title":"World J. Stem Cells"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e14952","DOI":"10.1016\/j.heliyon.2023.e14952","article-title":"FGF21\/FGFR1-\u03b2-KL cascade in cardiomyocytes modulates angiogenesis and inflammation under metabolic stress","volume":"9","author":"Kaur","year":"2023","journal-title":"Heliyon"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1038\/nmeth.2999","article-title":"Chemically defined generation of human cardiomyocytes","volume":"11","author":"Burridge","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1161\/CIRCRESAHA.114.300558","article-title":"Engineering adolescence","volume":"114","author":"Yang","year":"2014","journal-title":"Circ. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1161\/CIRCRESAHA.118.313249","article-title":"Metabolic maturation of human pluripotent stem Cell-Derived cardiomyocytes by inhibition of HIF1A and LDHA","volume":"123","author":"Hu","year":"2018","journal-title":"Circ. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.ceb.2010.05.004","article-title":"Cholesterol, the central lipid of mammalian cells","volume":"22","author":"Maxfield","year":"2010","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/BJ20110162","article-title":"Assessing mitochondrial dysfunction in cells","volume":"435","author":"Brand","year":"2011","journal-title":"Biochem. J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S1357-2725(03)00173-0","article-title":"The role of scavenger receptor class B type I (SR-BI) in lipid trafficking","volume":"36","author":"Rhainds","year":"2003","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1161\/CIRCRESAHA.117.311920","article-title":"Thyroid and glucocorticoid hormones promote functional T-Tubule development in Human-Induced pluripotent stem Cell\u2013Derived cardiomyocytes","volume":"121","author":"Parikh","year":"2017","journal-title":"Circ. Res."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Dudek, J. (2017). Role of Cardiolipin in Mitochondrial Signaling Pathways. Front. Cell Dev. Biol., 5.","DOI":"10.3389\/fcell.2017.00090"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1194\/jlr.R300004-JLR200","article-title":"Global analyses of cellular lipidomes directly from crude extracts of biological samples by ESI mass spectrometry: A bridge to lipidomics","volume":"44","author":"Han","year":"2003","journal-title":"J. Lipid Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nri.2017.21","article-title":"Mitochondrial DNA in innate immune responses and inflammatory pathology","volume":"17","author":"West","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1097\/FJC.0b013e318247f642","article-title":"Induced Pluripotent stem cells as a disease modeling and drug screening platform","volume":"60","author":"Ebert","year":"2012","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3012","DOI":"10.1038\/s41467-025-58301-8","article-title":"Medium from human iPSC-derived primitive macrophages promotes adult cardiomyocyte proliferation and cardiac regeneration","volume":"16","author":"Xiao","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1161\/ATVBAHA.114.303533","article-title":"Impact of phospholipid transfer protein on nascent high-density lipoprotein formation and remodeling","volume":"34","author":"Ji","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.bbalip.2004.12.011","article-title":"Anti-inflammatory effects of phospholipid transfer protein (PLTP) deficiency in mice","volume":"1733","author":"Schlitt","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Badran, A., Nasser, S.A., Mesmar, J., El-Yazbi, A.F., Bitto, A., Fardoun, M.M., Baydoun, E., and Eid, A.H. (2020). Reactive Oxygen Species: Modulators of Phenotypic Switch of Vascular Smooth Muscle Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228764"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1016\/j.bbamcr.2011.06.013","article-title":"PLTP regulates STAT3 and NF\u03baB in differentiated THP1 cells and human monocyte-derived macrophages","volume":"1813","author":"Vuletic","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13098-025-02065-0","article-title":"Lipid metabolism-inflammation crosstalk and risk of incident cancer, cardiovascular diseases, and stroke among individuals with prediabetes: Findings from a nationwide, population based, prospective cohort study","volume":"18","author":"Li","year":"2026","journal-title":"Diabetol Metab Syndr."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1161\/ATVBAHA.111.224881","article-title":"Mechanisms of ER stress-induced apoptosis in atherosclerosis","volume":"31","author":"Scull","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Newport, M.T., and Dayrit, F.M. (2024). The Lipid-Heart Hypothesis and the Keys Equation Defined the Dietary Guidelines but Ignored the Impact of Trans-Fat and High Linoleic Acid Consumption. Nutrients, 16.","DOI":"10.20944\/preprints202404.0788.v1"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3617\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:29:58Z","timestamp":1776673798000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,18]]},"references-count":105,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083617"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083617","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,18]]}}}