{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:39Z","timestamp":1792789119714,"version":"4.5.0"},"reference-count":84,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Alabama at Birmingham","id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Lipid homeostasis is essential for maintaining cellular function and metabolic balance in all organisms, and its dysregulation can contribute to hypercholesterolemia, atherosclerosis, and cardiovascular disease. Adverse health outcomes are associated with elevated levels of low-density lipoprotein cholesterol (LDL-C), retention of which causes macrophages to transition into foam cells, leading to widespread inflammation, cardiovascular disease, and atherosclerosis. Statins (HMG-CoA reductase inhibitors) are considered the gold standard for LDL and very-low-density lipoprotein (VLDL) reduction, yet they exhibit side effects like myalgia and insulin resistance. Apolipoprotein E (apo E)-based lipid-binding synthetic mimetic peptides have been shown to clear cholesterol from the blood through canonical hepatic pathways such as HSPG receptors and are currently being studied to reduce plasma cholesterol. This review examines the development, biological properties, and therapeutic potential of the apo E mimetic peptide AEM-28. AEM-28 reduces atherogenic lipoproteins from plasma efficiently in multiple preclinical models as well as Phase I clinical trials in humans, where general tolerance of the treatment was observed. AEM-28 utilizes a unique mechanism of action that involves binding to atherogenic lipoproteins with multiple receptor-binding domains, facilitating enhanced clearance via the highly abundant heparan sulfate proteoglycans on hepatocytes. These attributes support the potential of AEM-28 as a complementary therapeutic or even an alternative for patients requiring LDL apheresis and those with hypercholesterolemia, atherosclerosis, or cardiovascular disease.<\/jats:p>","DOI":"10.3390\/biom16091352","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:03:17Z","timestamp":1789632197000},"page":"1352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Apolipoprotein E Mimetic Peptide-Mediated Modulation of Lipid Homeostasis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3628-1004","authenticated-orcid":false,"given":"Dilan R.","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7609-8313","authenticated-orcid":false,"given":"Cole L.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Clinical and Diagnostic Science, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. M.","family":"Anantharamaiah","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0379-5534","authenticated-orcid":false,"given":"Stephen G.","family":"Aller","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s41043-025-01054-3","article-title":"Global prevalence of dyslipidemias in the general adult population: A systematic review and meta-analysis","volume":"44","year":"2025","journal-title":"J. Health Popul. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1016\/j.jacc.2014.01.060","article-title":"The severe hypercholesterolemia phenotype: Clinical diagnosis, management, and emerging therapies","volume":"63","author":"Sniderman","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.chemphyslip.2016.05.003","article-title":"The role of cholesterol in membrane fusion","volume":"199","author":"Yang","year":"2016","journal-title":"Chem. Phys. Lipids"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s43556-025-00321-3","article-title":"Cholesterol metabolism: Molecular mechanisms, biological functions, diseases, and therapeutic targets","volume":"6","author":"Cui","year":"2025","journal-title":"Mol. Biomed."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e2122584119","DOI":"10.1073\/pnas.2122584119","article-title":"Cellular itinerary of LDL cholesterol","volume":"119","author":"Vance","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kounatidis, D., Vallianou, N.G., Poulaki, A., Evangelopoulos, A., Panagopoulos, F., Stratigou, T., Geladari, E., Karampela, I., and Dalamaga, M. (2024). ApoB100 and Atherosclerosis: What\u2019s New in the 21st Century?. Metabolites, 14.","DOI":"10.3390\/metabo14020123"},{"key":"ref_7","unstructured":"Juarez Casso, F.M., and Farzam, K. (2026). Biochemistry, Very Low Density Lipoprotein. StatPearls, StatPearls."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e98045","DOI":"10.1172\/jci.insight.98045","article-title":"Apolipoproteins E and CIII interact to regulate HDL metabolism and coronary heart disease risk","volume":"3","author":"Morton","year":"2018","journal-title":"JCI Insight"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13024-020-00413-4","article-title":"APOE2: Protective mechanism and therapeutic implications for Alzheimer\u2019s disease","volume":"15","author":"Li","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"NS20180203","DOI":"10.1042\/NS20180203","article-title":"The role of APOE4 in Alzheimer\u2019s disease: Strategies for future therapeutic interventions","volume":"3","author":"Hunsberger","year":"2019","journal-title":"Neuronal Signal."},{"key":"ref_11","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_12","first-page":"100042","article-title":"Structure and intermolecular interactions in spheroidal high-density lipoprotein subpopulations","volume":"5","author":"Malajczuk","year":"2021","journal-title":"J. Struct. Biol. X"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100786","DOI":"10.1016\/j.jlr.2025.100786","article-title":"Lecithin:cholesterol acyltransferase binds a discontinuous binding site on adjacent apolipoprotein A-I belts in HDL","volume":"66","author":"Coleman","year":"2025","journal-title":"J. Lipid Res."},{"key":"ref_14","first-page":"e48865","article-title":"Lipoproteins and Their Effects on the Cardiovascular System","volume":"15","author":"Das","year":"2023","journal-title":"Cureus"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Gusev, E., and Sarapultsev, A. (2023). Atherosclerosis and Inflammation: Insights from the Theory of General Pathological Processes. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097910"},{"key":"ref_16","unstructured":"Feingold, K.R., Adler, R.A., Ahmed, S.F., Anawalt, B., Blackman, M.R., Chrousos, G., Corpas, E., de Herder, W.W., Dhatariya, K., and Dungan, K. (2000). The Role of Lipids and Lipoproteins in Atherosclerosis. Endotext, MDText.com, Inc."},{"key":"ref_17","first-page":"2537","article-title":"Heterogeneity of immune cells in human atherosclerosis revealed by scRNA-Seq","volume":"117","author":"Vallejo","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Xiong, J., Li, Z., Tang, H., Duan, Y., Ban, X., Xu, K., Guo, Y., and Tu, Y. (2023). Bulk and single-cell characterisation of the immune heterogeneity of atherosclerosis identifies novel targets for immunotherapy. BMC Biol., 21.","DOI":"10.1186\/s12915-023-01540-2"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s11883-026-01432-0","article-title":"Single-cell Technologies in Atherosclerosis: Uncovering Cellular Heterogeneity, Mechanisms, and Therapeutic Opportunities","volume":"28","author":"Serrano","year":"2026","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41392-023-01687-y","article-title":"The role of inflammasomes in human diseases and their potential as therapeutic targets","volume":"9","author":"Yao","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"141","DOI":"10.4161\/chan.20292","article-title":"Macrophage function in atherosclerosis: Potential roles of TRP channels","volume":"6","author":"Tano","year":"2012","journal-title":"Channels"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"212525","DOI":"10.7573\/dic.212525","article-title":"High-density lipoprotein (HDL) functionality and its relevance to atherosclerotic cardiovascular disease","volume":"7","author":"Kosmas","year":"2018","journal-title":"Drugs Context"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"491","DOI":"10.14336\/AD.2021.0929","article-title":"The Functional Role of Lipoproteins in Atherosclerosis: Novel Directions for Diagnosis and Targeting Therapy","volume":"13","author":"Lu","year":"2022","journal-title":"Aging Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Poznyak, A.V., Bharadwaj, D., Prasad, G., Grechko, A.V., Sazonova, M.A., and Orekhov, A.N. (2021). Anti-Inflammatory Therapy for Atherosclerosis: Focusing on Cytokines. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22137061"},{"key":"ref_25","first-page":"e63078","article-title":"New Insights Into the Treatment of Hyperlipidemia: Pharmacological Updates and Emerging Treatments","volume":"16","author":"Abbasi","year":"2024","journal-title":"Cureus"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wolkowicz, P., White, C.R., and Anantharamaiah, G.M. (2021). Apolipoprotein Mimetic Peptides: An Emerging Therapy against Diabetic Inflammation and Dyslipidemia. Biomolecules, 11.","DOI":"10.3390\/biom11050627"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1001\/jama.2022.12138","article-title":"Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: A Systematic Review for the U.S. Preventive Services Task Force","volume":"328","author":"Chou","year":"2022","journal-title":"JAMA"},{"key":"ref_28","unstructured":"Pokhrel, B., Pellegrini, M.V., and Levine, S.N. (2026). PCSK9 Inhibitors. StatPearls, StatPearls."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12944-020-01427-z","article-title":"LDL-cholesterol change and goal attainment following statin intensity titration among Asians in primary care: A retrospective cohort study","volume":"20","author":"Fang","year":"2021","journal-title":"Lipids Health Dis."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Anantharamaiah, G.M., and Goldberg, D. (2015). Apolipoprotein Mimetics in the Management of Human Disease, Adis. [1st ed.].","DOI":"10.1007\/978-3-319-17350-4"},{"key":"ref_31","first-page":"e202132","article-title":"From Fleming to Endo: The discovery of statins","volume":"2021","author":"Chester","year":"2021","journal-title":"Glob. Cardiol. Sci. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.medcli.2017.11.030","article-title":"Statins: Pros and cons","volume":"150","author":"Mammen","year":"2018","journal-title":"Med. Clin."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1007\/s00204-023-03492-6","article-title":"Understanding the molecular mechanisms of statin pleiotropic effects","volume":"97","author":"German","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.tcm.2019.01.001","article-title":"Effect of statins on atherosclerotic plaque","volume":"29","author":"Almeida","year":"2019","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1001\/jamacardio.2021.3055","article-title":"Association of Statin Treatment with Progression of Coronary Atherosclerotic Plaque Composition","volume":"6","author":"Gianni","year":"2021","journal-title":"JAMA Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"209","DOI":"10.2174\/1573403X13666170426104611","article-title":"The Anti-Inflammatory Effects of Statins on Coronary Artery Disease: An Updated Review of the Literature","volume":"13","author":"Diamantis","year":"2017","journal-title":"Curr. Cardiol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3288","DOI":"10.1093\/cvr\/cvac020","article-title":"Side effects of statins: From pathophysiology and epidemiology to diagnostic and therapeutic implications","volume":"118","author":"Ruscica","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1136\/heartjnl-2018-314253","article-title":"Sub-optimal cholesterol response to initiation of statins and future risk of cardiovascular disease","volume":"105","author":"Akyea","year":"2019","journal-title":"Heart"},{"key":"ref_39","first-page":"343","article-title":"The discovery of PCSK9 inhibitors: A tale of creativity and multifaceted translational research","volume":"2013","author":"Elguindy","year":"2013","journal-title":"Glob. Cardiol. Sci. Pract."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.3909\/ricm19S1S0002","article-title":"PCSK9 Inhibitors: Mechanism of Action, Efficacy, and Safety","volume":"19","author":"Roth","year":"2018","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e023328","DOI":"10.1161\/JAHA.121.023328","article-title":"Effects of PCSK9 Targeting: Alleviating Oxidation, Inflammation, and Atherosclerosis","volume":"11","author":"Punch","year":"2022","journal-title":"J. Am. Heart Assoc."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Basiak, M., Hachula, M., Kosowski, M., Machnik, G., Maliglowka, M., Dziubinska-Basiak, M., Krysiak, R., and Okopien, B. (2023). The Effect of PCSK9 Inhibition on the Stabilization of Atherosclerotic Plaque Determined by Biochemical and Diagnostic Imaging Methods. Molecules, 28.","DOI":"10.3390\/molecules28155928"},{"key":"ref_43","first-page":"191","article-title":"Safety and Tolerability of PCSK9 Inhibitors: Current Insights","volume":"12","author":"Kosmas","year":"2020","journal-title":"Clin. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1161\/CIRCULATIONAHA.121.057631","article-title":"Beyond 10-Year Risk: A Cost-Effectiveness Analysis of Statins for the Primary Prevention of Cardiovascular Disease","volume":"145","author":"Lewsey","year":"2022","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8129513","DOI":"10.1155\/2022\/8129513","article-title":"Advantages and Disadvantages of Inclisiran: A Small Interfering Ribonucleic Acid Molecule Targeting PCSK9\u2014A Narrative Review","volume":"2022","author":"Mercep","year":"2022","journal-title":"Cardiovasc. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2023-12-3","DOI":"10.7573\/dic.2023-12-3","article-title":"Inclisiran for the treatment of hypercholesterolaemia","volume":"13","author":"Marrs","year":"2024","journal-title":"Drugs Context"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100701","DOI":"10.1016\/j.ajpc.2024.100701","article-title":"Advances in targeting LDL cholesterol: PCSK9 inhibitors and beyond","volume":"19","author":"Safarova","year":"2024","journal-title":"Am. J. Prev. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s11883-019-0787-5","article-title":"Current Role of Lipoprotein Apheresis","volume":"21","author":"Thompson","year":"2019","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1161\/CIRCULATIONAHA.104.497107","article-title":"Apolipoprotein E mimetic Peptide dramatically lowers plasma cholesterol and restores endothelial function in watanabe heritable hyperlipidemic rabbits","volume":"111","author":"Gupta","year":"2005","journal-title":"Circulation"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1161\/01.ATV.0000165694.39518.95","article-title":"Apolipoprotein A-I mimetic peptides","volume":"25","author":"Navab","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0022-2275(20)31163-9","article-title":"A new synthetic class A amphipathic peptide analogue protects mice from diet-induced atherosclerosis","volume":"42","author":"Garber","year":"2001","journal-title":"J. Lipid Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.arcmed.2015.05.012","article-title":"Lipid-free Apolipoprotein A-I Structure: Insights into HDL Formation and Atherosclerosis Development","volume":"46","author":"Mei","year":"2015","journal-title":"Arch. Med. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6511","DOI":"10.1074\/jbc.M511475200","article-title":"Association of a model class A (apolipoprotein) amphipathic \u03b1 helical peptide with lipid: High resolution NMR studies of peptide.lipid discoidal complexes","volume":"281","author":"Mishra","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1016\/S0022-2275(20)37143-1","article-title":"Interaction of class A amphipathic helical peptides with phospholipid unilamellar vesicles","volume":"38","author":"Gazzara","year":"1997","journal-title":"J. Lipid Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.amjcard.2011.03.054","article-title":"Relation of increased prebeta-1 high-density lipoprotein levels to risk of coronary heart disease","volume":"108","author":"Guey","year":"2011","journal-title":"Am. J. Cardiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1097\/MOL.0000000000000444","article-title":"Cholesterol reduction and macrophage function: Role of paraoxonases","volume":"28","author":"White","year":"2017","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1096\/fj.10-165670","article-title":"4F Peptide reduces nascent atherosclerosis and induces natural antibody production in apolipoprotein E-null mice","volume":"25","author":"Wool","year":"2011","journal-title":"FASEB J."},{"key":"ref_58","first-page":"53","article-title":"Toward the design of peptide mimics of antiatherogenic apolipoproteins A-I and E","volume":"81","author":"Anantharamaiah","year":"2001","journal-title":"Curr. Sci. India"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1146\/annurev.nutr.19.1.141","article-title":"The mammalian low-density lipoprotein receptor family","volume":"19","author":"Hussain","year":"1999","journal-title":"Annu. Rev. Nutr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.cellsig.2018.11.022","article-title":"Heparan sulfate proteoglycan\u2014A common receptor for diverse cytokines","volume":"54","author":"Xie","year":"2019","journal-title":"Cell. Signal."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1042\/BJ20041536","article-title":"Orientation and mode of lipid-binding interaction of human apolipoprotein E C-terminal domain","volume":"387","author":"Raussens","year":"2005","journal-title":"Biochem. J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1089\/neu.2006.0192","article-title":"COG1410, a novel apolipoprotein E-based peptide, improves functional recovery in a murine model of traumatic brain injury","volume":"24","author":"Laskowitz","year":"2007","journal-title":"J. Neurotrauma"},{"key":"ref_63","first-page":"15","article-title":"The Apolipoprotein E Mimetic Peptide AEM-2 Attenuates Mitochondrial Injury and Apoptosis in Human THP-1 Macrophages","volume":"19","author":"Datta","year":"2018","journal-title":"Curr. Top. Pept. Protein Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.mcna.2020.02.011","article-title":"Sepsis and Septic Shock\u2014Basics of diagnosis, pathophysiology and clinical decision making","volume":"104","author":"Font","year":"2020","journal-title":"Med. Clin. N. Am."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1016\/j.bbalip.2014.07.018","article-title":"Apolipoprotein E derived HDL mimetic peptide ATI-5261 promotes nascent HDL formation and reverse cholesterol transport In Vitro","volume":"1841","author":"Hafiane","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.atherosclerosis.2012.05.040","article-title":"Apolipoprotein E mimetic is more effective than apolipoprotein A-I mimetic in reducing lesion formation in older female apo E null mice","volume":"224","author":"Nayyar","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1021\/bi991209w","article-title":"The receptor binding domain of apolipoprotein E, linked to a model class A amphipathic helix, enhances internalization and degradation of LDL by fibroblasts","volume":"39","author":"Datta","year":"2000","journal-title":"Biochemistry"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1161\/CIRCRESAHA.124.323578","article-title":"Pathways and Molecular Mechanisms Governing LDL Receptor Regulation","volume":"136","author":"Schmidt","year":"2025","journal-title":"Circ. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"S183","DOI":"10.1194\/jlr.R800069-JLR200","article-title":"Apolipoprotein E: Structure determines function, from atherosclerosis to Alzheimer\u2019s disease to AIDS","volume":"50","author":"Mahley","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/S0022-2275(20)31620-5","article-title":"Cationic domain 141-150 of apoE covalently linked to a class A amphipathic helix enhances atherogenic lipoprotein metabolism In Vitro and In Vivo","volume":"42","author":"Datta","year":"2001","journal-title":"J. Lipid Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0021-9150(03)00101-1","article-title":"Effect of an arginine-rich amphipathic helical peptide on plasma cholesterol in dyslipidemic mice","volume":"168","author":"Garber","year":"2003","journal-title":"Atherosclerosis"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.atherosclerosis.2012.10.064","article-title":"Two apolipoprotein E mimetic peptides with similar cholesterol reducing properties exhibit differential atheroprotective effects in LDL-R null mice","volume":"227","author":"Handattu","year":"2013","journal-title":"Atherosclerosis"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1161\/ATVBAHA.112.300282","article-title":"High-density lipoprotein and 4F peptide reduce systemic inflammation by modulating intestinal oxidized lipid metabolism: Novel hypotheses and review of literature","volume":"32","author":"Navab","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"211","DOI":"10.2165\/00129784-200404040-00002","article-title":"The role of paraoxonase 1 activity in cardiovascular disease: Potential for therapeutic intervention","volume":"4","author":"Mackness","year":"2004","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/ki.2009.177","article-title":"In vitro stimulation of HDL anti-inflammatory activity and inhibition of LDL pro-inflammatory activity in the plasma of patients with end-stage renal disease by an apoA-1 mimetic peptide","volume":"76","author":"Vaziri","year":"2009","journal-title":"Kidney Int."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Altyar, A.E., Bhardwaj, S., Ghaboura, N., Kaushik, P., Alenezi, S.K., Mantargi, M.J.S., and Afzal, M. (2025). Role of IL-2, IL-6, and TNF-\u03b1 as Potential Biomarkers in Ischemic Heart Disease: A Comparative Study of Patients with CAD and Non-CAD. Med. Sci., 13.","DOI":"10.3390\/medsci13020040"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5654","DOI":"10.1074\/jbc.274.9.5654","article-title":"Mitochondrial depolarization accompanies cytochrome c release during apoptosis in PC6 cells","volume":"274","author":"Heiskanen","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1161\/ATVBAHA.111.224873","article-title":"Apoptotic cell death and efferocytosis in atherosclerosis","volume":"32","author":"Tedgui","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1177\/1753425913514621","article-title":"Comparison of anti-endotoxin activity of apoE and apoA mimetic derivatives of a model amphipathic peptide 18A","volume":"20","author":"Sharifov","year":"2014","journal-title":"Innate Immun."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"(2012). The tale of the Watanabe rabbit. Lab Anim., 41, 277.","DOI":"10.1038\/laban1012-277"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S0021-9150(98)00098-7","article-title":"Impaired endothelium-dependent acetylcholine-induced coronary artery relaxation in patients with high serum remnant lipoprotein particles","volume":"139","author":"Inoue","year":"1998","journal-title":"Atherosclerosis"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1194\/jlr.M085985","article-title":"Novel fatty acyl apoE mimetic peptides have increased potency to reduce plasma cholesterol in mice and macaques","volume":"59","author":"Anantharamaiah","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_83","unstructured":"(2026, September 01). Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia, Available online: https:\/\/clinicaltrials.gov\/study\/NCT02100839."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0168-3659(01)00552-1","article-title":"Sustained-delivery of an apolipoproteinE-peptidomimetic using multivesicular liposomes lowers serum cholesterol levels","volume":"79","author":"Ramprasad","year":"2002","journal-title":"J. Control. Release"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/9\/1352\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:19:49Z","timestamp":1789791589000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/9\/1352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":84,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["biom16091352"],"URL":"https:\/\/doi.org\/10.3390\/biom16091352","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]}}}