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We also showed that, in mice, it ameliorates hepatic hallmarks of non-alcoholic steatohepatitis (NASH), including inflammation and fibrosis, and reduces adipose tissue inflammation. Here, we aim to investigate the effects of Oxy210 on atherosclerosis, an inflammatory disease of the large arteries that is linked to NASH in epidemiologic studies, shares many of the same risk factors, and is the major cause of mortality in people with NASH. Methods: Oxy210 was studied in vivo in APOE*3-Leiden.CETP mice, a humanized mouse model for both NASH and atherosclerosis, in which symptoms are induced by consumption of a high fat, high cholesterol \u201cWestern\u201d diet (WD). Oxy210 was also studied in vitro using two cell types that are important in atherogenesis: human aortic endothelial cells (HAECs) and macrophages treated with atherogenic and inflammatory agents. Results: Oxy210 reduced atherosclerotic lesion formation by more than 50% in hyperlipidemic mice fed the WD for 16 weeks. This was accompanied by reduced plasma cholesterol levels and reduced macrophages in lesions. In HAECs and macrophages, Oxy210 reduced the expression of key inflammatory markers associated with atherosclerosis, including interleukin-1 beta (IL-1\u03b2), interleukin-6 (IL-6), tumor necrosis factor-\u03b1 (TNF-\u03b1), chemokine (C-C motif) ligand 2 (CCL2), vascular cell adhesion molecule-1 (VCAM-1), and E-Selectin. In addition, cholesterol efflux was significantly enhanced in macrophages treated with Oxy210. Conclusions: These findings suggest that Oxy210 could be a drug candidate for targeting both NASH and atherosclerosis, as well as chronic inflammation associated with the manifestations of metabolic syndrome.<\/jats:p>","DOI":"10.3390\/cells13191632","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T08:09:52Z","timestamp":1727683792000},"page":"1632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Anti-Inflammatory Oxysterol, Oxy210, Inhibits Atherosclerosis in Hyperlipidemic Mice and Inflammatory Responses of Vascular Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Frank","family":"Stappenbeck","sequence":"first","affiliation":[{"name":"MAX BioPharma Inc., Santa Monica, CA 90404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"MAX BioPharma Inc., Santa Monica, CA 90404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyesh K.","family":"Sinha","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon T.","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"Farahi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigora","family":"Mukhamedova","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6803-3533","authenticated-orcid":false,"given":"Andrew","family":"Fleetwood","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7039-7777","authenticated-orcid":false,"given":"Andrew J.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8366-3832","authenticated-orcid":false,"given":"Dmitri","family":"Sviridov","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia"},{"name":"Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 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atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.cell.2022.04.004","article-title":"Atherosclerosis: Recent developments","volume":"185","author":"Lusis","year":"2022","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1016\/j.jacc.2019.07.061","article-title":"From Focal Lipid Storage to Systemic Inflammation: JACC Review Topic of the Week","volume":"74","author":"Libby","year":"2019","journal-title":"JACC"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1161\/ATVBAHA.108.179705","article-title":"Inflammation in atherosclerosis","volume":"32","author":"Libby","year":"2012","journal-title":"ATVB"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.atherosclerosis.2018.07.014","article-title":"Role of inflammation in the pathogenesis of atherosclerosis and therapeutic interventions","volume":"276","author":"Raggi","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.ahj.2004.07.041","article-title":"Atorvastatin has an important acute anti-inflammatory effect in patients with acute coronary syndrome: Results of a randomized, double-blind, placebo-controlled study","volume":"149","author":"Macin","year":"2005","journal-title":"Am. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.2174\/138161212799504803","article-title":"Statins as anti-inflammatory agents in atherogenesis: Molecular mechanisms and lessons from the recent clinical trials","volume":"18","author":"Antonopoulos","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s11883-012-0291-7","article-title":"How do we improve patient compliance and adherence to long-term statin therapy?","volume":"15","author":"Maningat","year":"2013","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Aday, A.W., and Ridker, P.M. (2018). Antiinflammatory Therapy in Clinical Care: The CANTOS Trial and Beyond. Front. Cardiovasc. Med., 5.","DOI":"10.3389\/fcvm.2018.00062"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez, L., Bulnes, J.F., Orellana, M.P., Mu\u00f1oz Venturelli, P., and Mart\u00ednez Rodriguez, G. (2022). The Role of Colchicine in Atherosclerosis: From Bench to Bedside. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14071395"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Czerniuk, M.R., Surma, S., Roma\u0144czyk, M., Nowak, J.M., Wojtowicz, A., and Filipiak, K.J. (2022). Unexpected Relationships: Periodontal Diseases: Atherosclerosis-Plaque Destabilization? From the Teeth to a Coronary Event. Biology, 11.","DOI":"10.3390\/biology11020272"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1177\/1559827617708991","article-title":"Advanced Glycation End Products and Risks for Chronic Diseases: Intervening Through Lifestyle Modification","volume":"13","author":"Prasad","year":"2017","journal-title":"Am. J. Lifestyle Med."},{"key":"ref_14","first-page":"42","article-title":"Non-Alcoholic Fatty Liver Disease, an Overview","volume":"18","author":"Nd","year":"2019","journal-title":"Integr. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1111\/j.1365-2036.2011.04724.x","article-title":"Systematic review: The epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults","volume":"34","author":"Vernon","year":"2011","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/s12944-015-0141-z","article-title":"Research advances in the relationship between nonalcoholic fatty liver disease and atherosclerosis","volume":"14","author":"Xu","year":"2015","journal-title":"Lipids Health Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.jhep.2016.04.005","article-title":"Non-alcoholic fatty liver disease and cardiovascular risk: Pathophysiological mechanisms and implications","volume":"65","author":"Francque","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5114\/ceh.2018.73155","article-title":"The influence of NAFLD on the risk of atherosclerosis and cardiovascular diseases","volume":"4","author":"Piekarska","year":"2018","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1161\/CIRCRESAHA.119.316337","article-title":"Nonalcoholic Fatty Liver Disease Pandemic Fuels the Upsurge in Cardiovascular Diseases","volume":"126","author":"Cai","year":"2020","journal-title":"Circ. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S300","DOI":"10.21037\/atm.2019.11.13","article-title":"New insights into the association between non-alcoholic fatty liver disease and atherosclerosis","volume":"7","author":"Qi","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Galatou, E., Mourelatou, E., Hatziantoniou, S., and Vizirianakis, I.S. (2022). Nonalcoholic Steatohepatitis (NASH) and Atherosclerosis: Explaining Their Pathophysiology, Association and the Role of Incretin-Based Drugs. Antioxidants, 11.","DOI":"10.3390\/antiox11061060"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s00392-020-01709-7","article-title":"NAFLD and cardiovascular diseases: A clinical review","volume":"110","author":"Kasper","year":"2021","journal-title":"Clin. Res. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.2147\/DDDT.S315724","article-title":"Non-Alcoholic Steatohepatitis (NASH)\u2014A Review of a Crowded Clinical Landscape, Driven by a Complex Disease","volume":"15","author":"Fraile","year":"2021","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1016\/S0140-6736(19)32517-6","article-title":"Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: A multicentre, randomised, double-blind, placebo-controlled, phase 2 trial","volume":"394","author":"Harrison","year":"2019","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"60","DOI":"10.17925\/EE.2023.19.1.60","article-title":"Resmetirom: An Orally Administered, Smallmolecule, Liver-directed, \u03b2-selective THR Agonist for the Treatment of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis","volume":"19","author":"Karim","year":"2023","journal-title":"touchREV Endocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jhep.2019.10.006","article-title":"Impact of obeticholic acid on the lipoprotein profile in patients with non-alcoholic steatohepatitis","volume":"72","author":"Siddiqui","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/s41591-022-02200-8","article-title":"Tropifexor for nonalcoholic steatohepatitis: An adaptive, randomized, placebo-controlled phase 2a\/b trial","volume":"29","author":"Sanyal","year":"2023","journal-title":"Nat. Med."},{"key":"ref_28","unstructured":"Feingold, K.R., Anawalt, B., Blackman, M.R., Boyce, A., Chrousos, G., Corpas, E., de Herder, W.W., Dhatariya, K., Dungan, K., and Hofland, J. (2024, August 26). The Role of Lipids and Lipoproteins in Atherosclerosis, Endotext, Updated 3 January 2019, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK343489\/."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/hep4.1801","article-title":"Role of Cholesterol-Associated Steatohepatitis in the Development of NASH","volume":"6","author":"Horn","year":"2022","journal-title":"Hepatol. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s12944-017-0579-2","article-title":"Current knowledge on the mechanism of atherosclerosis and pro-atherosclerotic properties of oxysterols","volume":"16","author":"Szterk","year":"2017","journal-title":"Lipids Health Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1194\/jlr.M093229","article-title":"Elevated oxysterol levels in human and mouse livers reflect nonalcoholic steatohepatitis","volume":"60","author":"Raselli","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.jcmgh.2021.12.018","article-title":"Hepatic Reduction in Cholesterol 25-Hydroxylase Aggravates Diet-induced Steatosis","volume":"13","author":"Dong","year":"2022","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1194\/jlr.RA120000924","article-title":"Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: A pathway for NAFL to NASH transition","volume":"61","author":"Kakiyama","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0021-9150(98)00196-8","article-title":"Oxysterols and atherosclerosis","volume":"142","author":"Brown","year":"1999","journal-title":"Atherosclerosis"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s10565-005-0141-2","article-title":"Comparison of the cytotoxic, pro-oxidant and inflammatory characteristics of different oxysterols","volume":"21","author":"Prunet","year":"2005","journal-title":"Cell Biol. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, F., Stappenbeck, F., Tang, L.-Y., Zhang, Y.E., Hui, S.T., Lusis, A.J., and Parhami, F. (2022). Oxy210, a Semi-Synthetic Oxysterol, Exerts Anti-Inflammatory Effects in Macrophages via Inhibition of Toll-like Receptor (TLR) 4 and TLR2 Signaling and Modulation of Macrophage Polarization. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105478"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8959","DOI":"10.1074\/jbc.M611741200","article-title":"Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent mesenchymal cells","volume":"282","author":"Dwyer","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/jcb.25668","article-title":"Inhibition of Pancreatic Cancer Cell-Induced Paracrine Hedgehog Signaling by Liver X Receptor Agonists and Oxy16, a Naturally Occurring Oxysterol","volume":"118","author":"Wang","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/nchembio.765","article-title":"Oxysterols are allosteric activators of the oncoprotein Smoothened","volume":"8","author":"Nachtergaele","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.neuropharm.2014.05.027","article-title":"Different oxysterols have opposing actions at N-methyl-D-aspartate receptors","volume":"85","author":"Linsenbardt","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.bbrc.2012.12.021","article-title":"27-hydroxycholesterol induces production of tumor necrosis factor-alpha from macrophages","volume":"430","author":"Kim","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Chang, J., Koseki, M., Saga, A., Kanno, K., Higo, T., Okuzaki, D., Okada, T., Inui, H., Tanaka, K., and Asaji, M. (2021). Dietary Oxysterol, 7-Ketocholesterol Accelerates Hepatic Lipid Accumulation and Macrophage Infiltration in Obese Mice. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.614692"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100486","DOI":"10.1016\/j.jlr.2023.100486","article-title":"25-Hydroxycholesterol in health and diseases","volume":"65","author":"Nguyen","year":"2024","journal-title":"J. Lipid Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s11745-010-3451-y","article-title":"Regulation of hepatocyte lipid metabolism and inflammatory response by 25-hydroxycholesterol and 25-hydroxycholesterol-3-sulfate","volume":"45","author":"Xu","year":"2010","journal-title":"Lipids"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E788","DOI":"10.1152\/ajpendo.00337.2011","article-title":"25-Hydroxycholesterol-3-sulfate attenuates inflammatory response via PPAR\u03b3 signaling in human THP-1 macrophages","volume":"302","author":"Xu","year":"2012","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.1111\/bph.15227","article-title":"Cholesterol and oxysterol sulfates: Pathophysiological roles and analytical challenges","volume":"178","author":"Sanchez","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E577","DOI":"10.1152\/ajpendo.00406.2023","article-title":"Larsucosterol: Endogenous epigenetic regulator for treating chronic and acute liver diseases","volume":"326","author":"Wang","year":"2024","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e00296","DOI":"10.1002\/edm2.296","article-title":"Oxy210, a novel inhibitor of hedgehog and TGF-\u03b2 signalling, ameliorates hepatic fibrosis and hypercholesterolemia in mice","volume":"4","author":"Hui","year":"2021","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1002\/hep.30113","article-title":"The Genetic Architecture of Diet-Induced Hepatic Fibrosis in Mice","volume":"68","author":"Hui","year":"2018","journal-title":"Hepatology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1161\/01.ATV.0000243925.65265.3c","article-title":"Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3-Leiden mice","volume":"26","author":"Westerterp","year":"2006","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Bennett, B.J., Davis, R.C., Civelek, M., Orozco, L., Wu, J., Qi, H., Pan, C., Packard, R.R.S., Eskin, E., and Yan, M. (2015). Genetic Architecture of Atherosclerosis in Mice: A Systems Genetics Analysis of Common Inbred Strains. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1005711"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Oppi, S., L\u00fcscher, T.F., and Stein, S. (2019). Mouse Models for Atherosclerosis Research-Which Is My Line?. Front. Cardiovasc. Med., 6.","DOI":"10.3389\/fcvm.2019.00046"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1042\/CS20210862","article-title":"Translating atherosclerosis research from bench to bedside: Navigating the barriers for effective preclinical drug discovery","volume":"136","author":"May","year":"2022","journal-title":"Clin. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Stappenbeck, F., Wang, F., Tang, L.Y., Zhang, Y.E., and Parhami, F. (2019). Inhibition of Non-Small Cell Lung Cancer Cells by Oxy210, an Oxysterol-Derivative that Antagonizes TGF\u03b2 and Hedgehog Signaling. Cells, 8.","DOI":"10.3390\/cells8101297"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1194\/jlr.M800095-JLR200","article-title":"Enhancing apolipoprotein A-I-dependent cholesterol efflux elevates cholesterol export from macrophages in vivo","volume":"49","author":"Mukhamedova","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1161\/ATVBAHA.118.311266","article-title":"Transcription Factor Zhx2 Deficiency Reduces Atherosclerosis and Promotes Macrophage Apoptosis in Mice","volume":"38","author":"Erbilgin","year":"2018","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1161\/ATVBAHA.120.315255","article-title":"Local M-CSF (Macrophage Colony-Stimulating Factor) Expression Regulates Macrophage Proliferation and Apoptosis in Atherosclerosis","volume":"41","author":"Sinha","year":"2021","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s00395-020-00838-4","article-title":"Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering","volume":"115","author":"Kornemann","year":"2020","journal-title":"Basic Res. Cardiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1038\/nm.3258","article-title":"Local proliferation dominates lesional macrophage accumulation in atherosclerosis","volume":"19","author":"Robbins","year":"2013","journal-title":"Nat. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"32921","DOI":"10.1074\/jbc.M306088200","article-title":"Oxidized phospholipids in minimally modified low density lipoprotein induce apoptotic signaling via activation of acid sphingomyelinase in arterial smooth muscle cells","volume":"278","author":"Loidl","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"12010","DOI":"10.1073\/pnas.96.21.12010","article-title":"Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils","volume":"96","author":"Leitinger","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1161\/CIRCRESAHA.111.256859","article-title":"Role of phospholipid oxidation products in atherosclerosis","volume":"111","author":"Lee","year":"2012","journal-title":"Circ. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"100499","DOI":"10.1016\/j.jlr.2024.100499","article-title":"The oxidized phospholipid PGPC impairs endothelial function by promoting endothelial cell ferroptosis via FABP3","volume":"65","author":"Chen","year":"2024","journal-title":"J. Lipid Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1189\/jlb.3VMA1215-579RR","article-title":"Oxidized phosphatidylcholine induces the activation of NLRP3 inflammasome in macrophages","volume":"101","author":"Yeon","year":"2017","journal-title":"J. Leukoc. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1161\/01.ATV.0000143933.20616.1b","article-title":"Inhibition of tumor necrosis factor-alpha reduces atherosclerosis in apolipoprotein E knockout mice","volume":"24","author":"Hovgaard","year":"2004","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3892\/etm.2015.2540","article-title":"Expression of vascular cell adhesion molecule-1 in the aortic tissues of atherosclerotic patients and the associated clinical implications","volume":"10","author":"Mu","year":"2015","journal-title":"Exp Ther Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1172\/JCI13005","article-title":"VCAM-1 is critical in atherosclerosis","volume":"107","author":"Ley","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.atherosclerosis.2012.11.029","article-title":"Evaluation of VCAM-1 antibodies as therapeutic agent for atherosclerosis in apolipoprotein E-deficient mice","volume":"226","author":"Park","year":"2013","journal-title":"Atherosclerosis"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1096\/fasebj.2022.36.S1.R6141","article-title":"The enigmatic role of VCAM-1 expressed by macrophages in mitochondrial metabolism and atherosclerosis","volume":"36","author":"Natarajan","year":"2022","journal-title":"FASEB J."},{"key":"ref_70","first-page":"1532832","article-title":"The Role of TLR2, TLR4, and TLR9 in the Pathogenesis of Atherosclerosis","volume":"2016","author":"Roshan","year":"2016","journal-title":"Int. J. Inflamm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/aps.2013.75","article-title":"Blocking TLR2 activity diminishes and stabilizes advanced atherosclerotic lesions in apolipoprotein E-deficient mice","volume":"34","author":"Wang","year":"2013","journal-title":"Acta Pharmacol Sin."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1161\/01.ATV.0000226553.01555.02","article-title":"Oxidized low-density lipoprotein correlates positively with toll-like receptor 2 and interferon regulatory factor-1 and inversely with superoxide dismutase-1 expression: Studies in hypercholesterolemic swine and THP-1 cells","volume":"26","author":"Holvoet","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1016\/j.freeradbiomed.2011.08.026","article-title":"Oxidized phospholipid-induced inflammation is mediated by Toll-like receptor 2","volume":"51","author":"Kadl","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_74","first-page":"RA145","article-title":"TGF-beta (transforming growth factor-beta) in chronic inflammatory conditions\u2014A new diagnostic and prognostic marker?","volume":"8","author":"Marek","year":"2002","journal-title":"Med. Sci. Monit."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1038\/s42255-019-0102-3","article-title":"Endothelial TGF-\u03b2 signalling drives vascular inflammation and atherosclerosis","volume":"1","author":"Chen","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1093\/cvr\/cvx202","article-title":"Beyond the matrix: MMP2 as critical regulator of inflammation-mediated vascular dysfunction","volume":"113","author":"Hoefer","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Olejarz, W., \u0141acheta, D., and Kubiak-Tomaszewska, G. (2020). Matrix Metalloproteinases as Biomarkers of Atherosclerotic Plaque Instability. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113946"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s11010-013-1911-4","article-title":"Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes","volume":"388","author":"Jayashree","year":"2014","journal-title":"Mol. Cell. Biochem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1136\/gutjnl-2018-317726","article-title":"Increased levels of systemic LPS-positive bacterial extracellular vesicles in patients with intestinal barrier dysfunction","volume":"69","author":"Tulkens","year":"2020","journal-title":"Gut"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1172\/JCI0216391","article-title":"Regulation and mechanisms of macrophage cholesterol efflux","volume":"110","author":"Tall","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1161\/CIRCULATIONAHA.111.066589","article-title":"Cholesterol efflux and atheroprotection: Advancing the concept of reverse cholesterol transport","volume":"125","author":"Rosenson","year":"2012","journal-title":"Circulation"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e024754","DOI":"10.1161\/JAHA.121.024754","article-title":"Antiatherosclerotic Effects of CSL112 Mediated by Enhanced Cholesterol Efflux Capacity","volume":"11","author":"Kingwell","year":"2022","journal-title":"J. Am. Hear. Assoc."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1161\/CIRCULATIONAHA.119.039476","article-title":"Apolipoprotein AI Promotes Atherosclerosis Regression in Diabetic Mice by Suppressing Myelopoiesis and Plaque Inflammation","volume":"140","author":"Barrett","year":"2019","journal-title":"Circulation"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Bhale, A.S., and Venkataraman, K. (2022). Leveraging knowledge of HDLs major protein ApoA1: Structure, function, mutations, and potential therapeutics. Biomed. Pharmacother., 154.","DOI":"10.1016\/j.biopha.2022.113634"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8264","DOI":"10.1073\/pnas.92.18.8264","article-title":"Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E","volume":"92","author":"Smith","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e74","DOI":"10.1161\/ATVBAHA.121.316093","article-title":"Emerging Concepts of Vascular Cell clonal expansion in atherosclerosis","volume":"42","author":"Misra","year":"2022","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Wang, F., Stappenbeck, F., and Parhami, F. (2023). Oxy210, a Semi-Synthetic Oxysterol, Inhibits Profibrotic Signaling in Cellular Models of Lung and Kidney Fibrosis. Pharmaceuticals, 16.","DOI":"10.3390\/ph16010114"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1017\/S0007114512001213","article-title":"Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia","volume":"108","author":"Moreira","year":"2012","journal-title":"Br. J. Nutr."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.biochi.2015.06.020","article-title":"Metabolic endotoxemia with obesity: Is it real and is it relevant?","volume":"124","author":"Boutagy","year":"2016","journal-title":"Biochimie"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Mohammad, S., and Thiemermann, C. (2021). Role of Metabolic Endotoxemia in Systemic Inflammation and Potential Interventions. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.594150"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1007\/s12011-023-03941-4","article-title":"Prophylactic and Therapeutic Efficacy of Boric Acid on Lipopolysaccharide-Induced Liver and Kidney Inflammation in Rats","volume":"202","author":"Kar","year":"2024","journal-title":"Biol. Trace Element Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1046\/j.1365-2249.2002.01956.x","article-title":"Differential effects of prophylactic, concurrent and therapeutic lactoferrin treatment on LPS-induced inflammatory responses in mice","volume":"130","author":"Kruzel","year":"2002","journal-title":"Clin. Exp. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Tang, L.-Y., Spezia, M., Chen, T., Shin, J.-H., Wang, F., Stappenbeck, F., Lebensohn, A.M., Parhami, F., and Zhang, Y.E. (2022). Oxysterol derivatives Oxy186 and Oxy210 inhibit WNT signaling in non-small cell lung cancer. Cell Biosci., 12.","DOI":"10.1186\/s13578-022-00857-9"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7874","DOI":"10.1021\/jm5006463","article-title":"Polypharmacology: Challenges and opportunities in drug discovery","volume":"57","author":"Anighoro","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Xu, S., and Tang, C. (2022). Cholesterol and Hedgehog Signaling: Mutual Regulation and Beyond. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.774291"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1002\/jcp.21303","article-title":"Cholesterol modulates cellular TGF-beta responsiveness by altering TGF-beta binding to TGF-beta receptors","volume":"215","author":"Chen","year":"2008","journal-title":"J. Cell. Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"741","DOI":"10.15252\/embr.201540081","article-title":"Wnt directs the endosomal flux of LDL-derived cholesterol and lipid droplet homeostasis","volume":"16","author":"Scott","year":"2015","journal-title":"EMBO Rep."},{"key":"ref_98","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_99","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1172\/JCI0216388","article-title":"Do oxysterols control cholesterol homeostasis?","volume":"110","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.tem.2011.12.002","article-title":"Oxysterols as non-genomic regulators of cholesterol homeostasis","volume":"23","author":"Bielska","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.jhep.2022.12.025","article-title":"Rational combination therapy for NASH: Insights from clinical trials and error","volume":"78","author":"Ratziu","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Dong, Q., Bao, H., Wang, J., Shi, W., Zou, X., Sheng, J., Gao, J., Guan, C., Xia, H., and Li, J. (2023). Liver fibrosis and MAFLD: The exploration of multi-drug combination therapy strategies. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1120621"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s42004-020-00411-z","article-title":"A triple farnesoid X receptor and peroxisome proliferator-activated receptor \u03b1\/\u03b4 activator reverses hepatic fibrosis in diet-induced NASH in mice","volume":"3","author":"Heitel","year":"2020","journal-title":"Commun. Chem."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/19\/1632\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:07:43Z","timestamp":1760112463000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/19\/1632"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,30]]},"references-count":103,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["cells13191632"],"URL":"https:\/\/doi.org\/10.3390\/cells13191632","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,30]]}}}