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Review

Lipid-laden foam cells in the pathology of atherosclerosis: shedding light on new therapeutic targets

, , , , & ORCID Icon
Pages 1231-1245 | Received 28 Jun 2023, Accepted 22 Nov 2023, Published online: 28 Nov 2023

References

  • Farzadfar F. Cardiovascular disease risk prediction models: challenges and perspectives. Lancet Glob Health. 2019 Oct;7(10):e1288–e1289. doi: 10.1016/S2214-109X(19)30365-1
  • Laurindo LF, de Carvalho GM, de Oliveira Zanuso B, et al. Curcumin-based nanomedicines in the treatment of inflammatory and immunomodulated diseases: an evidence-based comprehensive Review. Pharmaceutics. 2023 Jan 10;15(1):229. doi: 10.3390/pharmaceutics15010229
  • Writing C, Lloyd-Jones DM, Morris PB, et al. ACC Expert consensus decision pathway on the role of non-statin therapies for LDL-Cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American college of cardiology task force on clinical Expert consensus documents. J Am Coll Cardiol. 2016 [2016 Jul 5];68(1):92–125. doi: 10.1016/j.jacc.2016.03.519
  • Lamb YN. Rosuvastatin/Ezetimibe: A Review in Hypercholesterolemia. Am J Cardiovasc Drugs. 2020 Aug;20(4):381–392. doi: 10.1007/s40256-020-00421-1
  • Masana Marin L, Plana Gil N. Bempedoic acid. Mechanism of action and pharmacokinetic and pharmacodynamic properties. Clin Investig Arterioscler. 2021 May;33(Suppl 1):53–57. doi: 10.1016/j.arteri.2021.02.012
  • Istvan ES, Deisenhofer J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science. 2001 May 11;292(5519):1160–1164. doi: 10.1126/science.1059344
  • Whayne TF Jr. PCSK9 inhibitors in the current management of atherosclerosis. Arch Cardiol Mex. 2017 Jan;87(1):43–48. doi: 10.1016/j.acmx.2016.11.013
  • Yurtseven E, Ural D, Baysal K, et al. An update on the role of PCSK9 in atherosclerosis. J Atheroscler Thromb. 2020 Sep 1;27(9):909–918. doi: 10.5551/jat.55400
  • Berberich AJ, Hegele RA. Lomitapide for the treatment of hypercholesterolemia. Expert Opin Pharmacother. 2017 Aug;18(12):1261–1268. doi: 10.1080/14656566.2017.1340941
  • Sosnowska B, Adach W, Surma S, et al. Evinacumab, an ANGPTL3 inhibitor, in the treatment of dyslipidemia. J Clin Med. 2022 Dec 25;12(1):168. doi: 10.3390/jcm12010168
  • Staels B, Dallongeville J, Auwerx J, et al. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation. 1998 Nov 10;98(19):2088–2093. doi: 10.1161/01.CIR.98.19.2088
  • Valanti EK, Dalakoura-Karagkouni K, Siasos G, et al. Advances in biological therapies for dyslipidemias and atherosclerosis. Metabolism. 2021 Mar;116:154461.
  • Robichaud S, Fairman G, Vijithakumar V, et al. Identification of novel lipid droplet factors that regulate lipophagy and cholesterol efflux in macrophage foam cells. Autophagy. 2021 Nov;17(11):3671–3689. doi: 10.1080/15548627.2021.1886839
  • Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol. 2013 Oct;13(10):709–721. doi: 10.1038/nri3520
  • Ding S, Lin N, Sheng X, et al. Melatonin stabilizes rupture-prone vulnerable plaques via regulating macrophage polarization in a nuclear circadian receptor RORalpha-dependent manner. J Pineal Res. 2019 Sep;67(2):e12581. doi: 10.1111/jpi.12581
  • Chen Z, Zhuo R, Zhao Y, et al. Oleoylethanolamide stabilizes atherosclerotic plaque through regulating macrophage polarization via AMPK-PPARalpha pathway. Biochem Biophys Res Commun. 2020 Apr 2;524(2):308–316. doi: 10.1016/j.bbrc.2020.01.103
  • Zhao Y, Yan L, Peng L, et al. Oleoylethanolamide alleviates macrophage formation via AMPK/PPARalpha/STAT3 pathway. Pharmacol Rep. 2018 Dec;70(6):1185–1194. doi: 10.1016/j.pharep.2018.06.006
  • Li B, Sheng Z, Liu C, et al. Kallistatin inhibits atherosclerotic inflammation by regulating macrophage polarization. Hum Gene Ther. 2019 Mar;30(3):339–351. doi: 10.1089/hum.2018.084
  • El Hadri K, Mahmood DF, Couchie D, et al. Thioredoxin-1 promotes anti-inflammatory macrophages of the M2 phenotype and antagonizes atherosclerosis. Arterioscler Thromb Vasc Biol. 2012 Jun;32(6):1445–1452. doi: 10.1161/ATVBAHA.112.249334
  • Guo M, Xiao J, Sheng X, et al. Ginsenoside Rg3 mitigates atherosclerosis progression in diabetic apoE-/- mice by skewing macrophages to the M2 phenotype. Front Pharmacol. 2018;9:464. doi: 10.3389/fphar.2018.00464
  • Zhang X, Liu MH, Qiao L, et al. Ginsenoside Rb1 enhances atherosclerotic plaque stability by skewing macrophages to the M2 phenotype. J Cell Mol Med. 2018 Jan;22(1):409–416. doi: 10.1111/jcmm.13329
  • Chen F, Guo N, Cao G, et al. Molecular analysis of curcumin-induced polarization of murine RAW264.7 macrophages. J Cardiovasc Pharmacol. 2014 Jun;63(6):544–552. doi: 10.1097/FJC.0000000000000079
  • Zhou Y, Zhang T, Wang X, et al. Curcumin modulates macrophage polarization through the inhibition of the toll-like receptor 4 expression and its signaling pathways. Cell Physiol Biochem. 2015;36(2):631–641. doi: 10.1159/000430126
  • Wang N, Zhang X, Ma Z, et al. Combination of tanshinone IIA and astragaloside IV attenuate atherosclerotic plaque vulnerability in ApoE(-/-) mice by activating PI3K/AKT signaling and suppressing TRL4/NF-kappaB signaling. Biomed Pharmacother. 2020 Mar;123:109729.
  • Aharoni S, Lati Y, Aviram M, et al. Pomegranate juice polyphenols induce a phenotypic switch in macrophage polarization favoring a M2 anti-inflammatory state. BioFactors. 2015 Jan;41(1):44–51. doi: 10.1002/biof.1199
  • Li J, Lei HT, Cao L, et al. Crocin alleviates coronary atherosclerosis via inhibiting lipid synthesis and inducing M2 macrophage polarization. Int Immunopharmacol. 2018 Feb;55:120–127.
  • Jin Z, Li J, Pi J, et al. Geniposide alleviates atherosclerosis by regulating macrophage polarization via the FOS/MAPK signaling pathway. Biomed Pharmacother. 2020 May;125:110015.
  • Liu Y, Wang X, Pang J, et al. Attenuation of atherosclerosis by protocatechuic acid via inhibition of M1 and promotion of M2 macrophage polarization. J Agric Food Chem. 2019 Jan 23;67(3):807–818. doi: 10.1021/acs.jafc.8b05719
  • Hara T, Fukuda D, Tanaka K, et al. Rivaroxaban, a novel oral anticoagulant, attenuates atherosclerotic plaque progression and destabilization in ApoE-deficient mice. Atherosclerosis. 2015 Oct;242(2):639–646. doi: 10.1016/j.atherosclerosis.2015.03.023
  • Singla DK, Johnson TA, Tavakoli Dargani Z. Exosome treatment enhances anti-inflammatory M2 macrophages and reduces inflammation-induced pyroptosis in doxorubicin-induced cardiomyopathy. Cells. 2019 Oct 9;8(10):1224. doi: 10.3390/cells8101224
  • Brenner C, Franz WM, Kuhlenthal S, et al. DPP-4 inhibition ameliorates atherosclerosis by priming monocytes into M2 macrophages. Int J Cardiol. 2015 Nov 15;199:163–169. doi: 10.1016/j.ijcard.2015.07.044
  • Derosa G, Ragonesi PD, Fogari E, et al. Sitagliptin added to previously taken antidiabetic agents on insulin resistance and lipid profile: a 2-year study evaluation. Fundam Clin Pharmacol. 2014 Apr;28(2):221–229. doi: 10.1111/fcp.12001
  • Skiba DS, Nosalski R, Mikolajczyk TP, et al. Anti-atherosclerotic effect of the angiotensin 1-7 mimetic AVE0991 is mediated by inhibition of perivascular and plaque inflammation in early atherosclerosis. Br J Pharmacol. 2017 Nov;174(22):4055–4069. doi: 10.1111/bph.13685
  • Shen L, Sun Z, Nie P, et al. Sulindac-derived retinoid X receptor-alpha modulator attenuates atherosclerotic plaque progression and destabilization in ApoE(-/-) mice. Br J Pharmacol. 2019 Jul;176(14):2559–2572. doi: 10.1111/bph.14682
  • Li J, Xue H, Li T, et al. Exosomes derived from mesenchymal stem cells attenuate the progression of atherosclerosis in ApoE(-/-) mice via miR-let7 mediated infiltration and polarization of M2 macrophage. Biochem Biophys Res Commun. 2019 Mar 19;510(4):565–572. doi: 10.1016/j.bbrc.2019.02.005
  • Ma J, Chen L, Zhu X, et al. Mesenchymal stem cell-derived exosomal miR-21a-5p promotes M2 macrophage polarization and reduces macrophage infiltration to attenuate atherosclerosis. Acta Biochim Biophys Sin (Shanghai). 2021 Aug 31;53(9):1227–1236. doi: 10.1093/abbs/gmab102
  • Tang D, Wang Y, Wijaya A, et al. ROS-responsive biomimetic nanoparticles for potential application in targeted anti-atherosclerosis. Regen Biomater. 2021 Aug;8(4):rbab033. doi: 10.1093/rb/rbab033
  • Gao C, Huang Q, Liu C, et al. Treatment of atherosclerosis by macrophage-biomimetic nanoparticles via targeted pharmacotherapy and sequestration of proinflammatory cytokines. Nat Commun. 2020 May 26;11(1):2622. doi: 10.1038/s41467-020-16439-7
  • Yu SS, Lau CM, Barham WJ, et al. Macrophage-specific RNA interference targeting via “click”, mannosylated polymeric micelles. Mol Pharm. 2013 Mar 4;10(3):975–987. doi: 10.1021/mp300434e
  • He H, Yuan Q, Bie J, et al. Development of mannose functionalized dendrimeric nanoparticles for targeted delivery to macrophages: use of this platform to modulate atherosclerosis. Transl Res. 2018 Mar;193:13–30.
  • Fang F, Xiao C, Li C, et al. Tuning macrophages for atherosclerosis treatment. Regen Biomater. 2023;10:rbac103. doi: 10.1093/rb/rbac103
  • Lewis DR, Petersen LK, York AW, et al. Sugar-based amphiphilic nanoparticles arrest atherosclerosis in vivo. Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):2693–2698. doi: 10.1073/pnas.1424594112
  • Zhang WL, Xiao Y, Liu JP, et al. Structure and remodeling behavior of drug-loaded high density lipoproteins and their atherosclerotic plaque targeting mechanism in foam cell model. Int J Pharm. 2011 Oct 31;419(1–2):314–321. doi: 10.1016/j.ijpharm.2011.07.039
  • Matoba T, Koga JI, Nakano K, et al. Nanoparticle-mediated drug delivery system for atherosclerotic cardiovascular disease. J Cardiol. 2017 Sep;70(3):206–211. doi: 10.1016/j.jjcc.2017.03.005
  • Gu X, Zhang W, Liu J, et al. Preparation and characterization of a lovastatin-loaded protein-free nanostructured lipid carrier resembling high-density lipoprotein and evaluation of its targeting to foam cells. AAPS Pharm Sci Tech. 2011 Dec;12(4):1200–1208. doi: 10.1208/s12249-011-9668-0
  • Zhao Y, Jiang C, He J, et al. Multifunctional dextran sulfate-coated reconstituted high density lipoproteins target macrophages and promote beneficial antiatherosclerotic mechanisms. Bioconjug Chem. 2017 Feb 15;28(2):438–448. doi: 10.1021/acs.bioconjchem.6b00600
  • Miao G, Zhao X, Chan SL, et al. Vascular smooth muscle cell c-fos is critical for foam cell formation and atherosclerosis. Metabolism. 2022 Jul;132:155213.
  • Farina FM, Hall IF, Serio S, et al. Mi R-128-3p is a novel regulator of vascular smooth muscle cell phenotypic switch and vascular diseases. Circ Res. 2020 Jun 5;126(12):e120–e135. doi: 10.1161/CIRCRESAHA.120.316489
  • Shankman LS, Gomez D, Cherepanova OA, et al. KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. Nat Med. 2015 Jun;21(6):628–637. doi: 10.1038/nm.3866
  • Ma WF, Hodonsky CJ, Turner AW, et al. Enhanced single-cell RNA-seq workflow reveals coronary artery disease cellular cross-talk and candidate drug targets. Atherosclerosis. 2022 Jan;340:12–22.
  • Pan H, Xue C, Auerbach BJ, et al. Single-cell genomics reveals a novel cell state during smooth muscle cell phenotypic switching and potential therapeutic targets for atherosclerosis in mouse and human. Circulation. 2020 Nov 24;142(21):2060–2075. doi: 10.1161/CIRCULATIONAHA.120.048378
  • Liu Y, Zheng B, Zhang XH, et al. Localization and function of KLF4 in cytoplasm of vascular smooth muscle cell. Biochem Biophys Res Commun. 2013 Jun 28;436(2):162–168. doi: 10.1016/j.bbrc.2013.05.067
  • Zheng B, Han M, Wen JK. Role of Kruppel-like factor 4 in phenotypic switching and proliferation of vascular smooth muscle cells. IUBMB Life. 2010 Feb;62(2):132–139. doi: 10.1002/iub.298
  • Jiang Y, Qian HY. Transcription factors: key regulatory targets of vascular smooth muscle cell in atherosclerosis. Mol Med. 2023 Jan 5;29(1):2. doi: 10.1186/s10020-022-00586-2
  • Xie Y, Martin KA. TCF21: flipping the phenotypic switch in SMC. Circ Res. 2020 Feb 14;126(4):530–532. doi: 10.1161/CIRCRESAHA.120.316533
  • Kusunoki J, Hansoty DK, Aragane K, et al. Acyl-CoA:cholesterol acyltransferase inhibition reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2001 May 29;103(21):2604–2609. doi: 10.1161/01.CIR.103.21.2604
  • Rong JX, Blachford C, Feig JE, et al. ACAT inhibition reduces the progression of preexisting, advanced atherosclerotic mouse lesions without plaque or systemic toxicity. Arterioscler Thromb Vasc Biol. 2013 Jan;33(1):4–12. doi: 10.1161/ATVBAHA.112.252056
  • Aragane K, Fujinami K, Kojima K, et al. ACAT inhibitor F-1394 prevents intimal hyperplasia induced by balloon injury in rabbits. J Lipid Res. 2001 Apr;42(4):480–488. doi: 10.1016/S0022-2275(20)31156-1
  • Chiwata T, Aragane K, Fujinami K, et al. Direct effect of an acyl-CoA: cholesterol acyltransferase inhibitor, F-1394, on atherosclerosis in apolipoprotein E and low density lipoprotein receptor double knockout mice. Br J Pharmacol. 2001 Aug;133(7):1005–1012. doi: 10.1038/sj.bjp.0704160
  • Kusunoki J, Aragane K, Kitamine T, et al. Hypocholesterolemic action and prevention of cholesterol absorption via the gut by F-1394, a potent acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor, in cholesterol diet-fed rats. Jpn J Pharmacol. 1995 Sep;69(1):53–60. doi: 10.1254/jjp.69.53
  • Amengual J, Ogando Y, Nikain C, et al. Short-term acyl-CoA: Cholesterol acyltransferase inhibition, combined with apoprotein A1 overexpression, promotes atherosclerosis inflammation resolution in mice. Mol Pharmacol. 2021 Mar;99(3):175–183. doi: 10.1124/molpharm.120.000108
  • Ramharack R, Spahr MA, Sekerke CS, et al. CI-1011 lowers lipoprotein(a) and plasma cholesterol concentrations in chow-fed cynomolgus monkeys. Atherosclerosis. 1998 Jan;136(1):79–87. doi: 10.1016/S0021-9150(97)00189-5
  • Burnett JR, Telford DE, Barrett PH, et al. The ACAT inhibitor avasimibe increases the fractional clearance rate of postprandial triglyceride-rich lipoproteins in miniature pigs. Biochim Biophys Acta. 2005 Dec 30;1738(1–3):10–18. doi: 10.1016/j.bbalip.2005.11.010
  • Burnett JR, Wilcox LJ, Telford DE, et al. Inhibition of ACAT by avasimibe decreases both VLDL and LDL apolipoprotein B production in miniature pigs. J Lipid Res. 1999 Jul;40(7):1317–1327. doi: 10.1016/S0022-2275(20)33494-5
  • Bocan TM, Krause BR, Rosebury WS, et al. The ACAT inhibitor avasimibe reduces macrophages and matrix metalloproteinase expression in atherosclerotic lesions of hypercholesterolemic rabbits. Arterioscler Thromb Vasc Biol. 2000 Jan;20(1):70–79. doi: 10.1161/01.ATV.20.1.70
  • Robertson DG, Breider MA, Milad MA. Preclinical safety evaluation of avasimibe in beagle dogs: an ACAT inhibitor with minimal adrenal effects. Toxicol Sci. 2001 Feb;59(2):324–334. doi: 10.1093/toxsci/59.2.324
  • Worthley SG, Helft G, Corti R, et al. Statin therapy alone and in combination with an acyl-CoA: cholesterol O-acyltransferase inhibitor on experimental atherosclerosis. Pathophysiol Haemost Thromb. 2007;36(1):9–17. doi: 10.1159/000112634
  • Terasaka N, Miyazaki A, Kasanuki N, et al. ACAT inhibitor pactimibe sulfate (CS-505) reduces and stabilizes atherosclerotic lesions by cholesterol-lowering and direct effects in apolipoprotein E-deficient mice. Atherosclerosis. 2007 Feb;190(2):239–247. doi: 10.1016/j.atherosclerosis.2006.03.007
  • Tardif JC, Gregoire J, L’Allier PL, et al. Effects of the acyl coenzyme A: cholesterol acyltransferase inhibitor avasimibe on human atherosclerotic lesions. Circulation. 2004 Nov 23;110(21):3372–3377. doi: 10.1161/01.CIR.0000147777.12010.EF
  • Nissen SE, Tuzcu EM, Brewer HB, et al. Effect of ACAT inhibition on the progression of coronary atherosclerosis. N Engl J Med. 2006 Mar 23;354(12):1253–1263. doi: 10.1056/NEJMoa054699
  • Meuwese MC, de Groot E, Duivenvoorden R, et al. ACAT inhibition and progression of carotid atherosclerosis in patients with familial hypercholesterolemia: the CAPTIVATE randomized trial. JAMA. 2009 Mar 18;301(11):1131–1139. doi: 10.1001/jama.301.11.1131
  • Xu J, Hu G, Lu M, et al. MiR-9 reduces human acyl-coenzyme a: cholesterol acyltransferase-1 to decrease THP-1 macrophage-derived foam cell formation. Acta Biochim Biophys Sin (Shanghai). 2013 Nov;45(11):953–962. doi: 10.1093/abbs/gmt096
  • Zhang R, Song B, Hong X, et al. microRNA-9 inhibits vulnerable plaque formation and vascular remodeling via suppression of the SDC2-dependent FAK/ERK signaling pathway in mice with atherosclerosis. Front Physiol. 2020;11:804. doi: 10.3389/fphys.2020.00804
  • Sekiya M, Osuga J, Nagashima S, et al. Ablation of neutral cholesterol ester hydrolase 1 accelerates atherosclerosis. Cell Metab. 2009 Sep;10(3):219–228. doi: 10.1016/j.cmet.2009.08.004
  • Gui Y, Zheng H, Cao RY. Foam cells in atherosclerosis: novel insights into its origins, consequences, and molecular mechanisms. Front Cardiovasc Med. 2022;9:845942. doi: 10.3389/fcvm.2022.845942
  • Li L, Wu F, Xie Y, et al. MiR-202-3p inhibits foam cell formation and is associated with coronary heart disease risk in a Chinese population. Int Heart J. 2020 Jan 31;61(1):153–159. doi: 10.1536/ihj.19-033
  • Ma X, Li SF, Qin ZS, et al. Propofol up-regulates expression of ABCA1, ABCG1, and SR-B1 through the PPARgamma/LXRalpha signaling pathway in THP-1 macrophage-derived foam cells. Cardiovasc Pathol. 2015 Jul;24(4):230–235. doi: 10.1016/j.carpath.2014.12.004
  • Hsu CP, Lin CH, Kuo CY. Endothelial-cell inflammation and damage by reactive oxygen species are prevented by propofol via ABCA1-mediated cholesterol efflux. Int J Med Sci. 2018;15(10):978–985. doi: 10.7150/ijms.24659
  • Chen X, Zhao Y, Guo Z, et al. Transcriptional regulation of ATP-binding cassette transporter A1 expression by a novel signaling pathway. J Biol Chem. 2011 Mar 18;286(11):8917–8923. doi: 10.1074/jbc.M110.214429
  • Chawla A, Boisvert WA, Lee CH, et al. A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell. 2001 Jan;7(1):161–171. doi: 10.1016/S1097-2765(01)00164-2
  • Costet P, Luo Y, Wang N, et al. Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J Biol Chem. 2000 Sep 8;275(36):28240–28245. doi: 10.1074/jbc.M003337200
  • Zeng L, Liao H, Liu Y, et al. Sterol-responsive element-binding protein (SREBP) 2 down-regulates ATP-binding cassette transporter A1 in vascular endothelial cells: a novel role of SREBP in regulating cholesterol metabolism. J Biol Chem. 2004 Nov 19;279(47):48801–48807. doi: 10.1074/jbc.M407817200
  • Bunay J, Fouache A, Trousson A, et al. Screening for liver X receptor modulators: where are we and for what use? Br J Pharmacol. 2021 Aug;178(16):3277–3293. doi: 10.1111/bph.15286
  • Chinetti G, Lestavel S, Bocher V, et al. PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med. 2001 Jan;7(1):53–58. doi: 10.1038/83348
  • Chen W, Wang S, Xing D. New horizons for the roles and association of APE1/Ref-1 and ABCA1 in atherosclerosis. J Inflamm Res. 2021;14:5251–5271. doi: 10.2147/JIR.S330147
  • Baldan A, Pei L, Lee R, et al. Impaired development of atherosclerosis in hyperlipidemic ldlr-/- and ApoE-/- mice transplanted with Abcg1-/- bone marrow. Arterioscler Thromb Vasc Biol. 2006 Oct;26(10):2301–2307. doi: 10.1161/01.ATV.0000240051.22944.dc
  • Demetz E, Tancevski I, Duwensee K, et al. Inhibition of hepatic scavenger receptor-class B type I by RNA interference decreases atherosclerosis in rabbits. Atherosclerosis. 2012 Jun;222(2):360–366. doi: 10.1016/j.atherosclerosis.2012.03.012
  • Van Eck M, Bos IS, Hildebrand RB, et al. Dual role for scavenger receptor class B, type I on bone marrow-derived cells in atherosclerotic lesion development. Am J Pathol. 2004 Sep;165(3):785–794. doi: 10.1016/S0002-9440(10)63341-X
  • Zhang W, Yancey PG, Su YR, et al. Inactivation of macrophage scavenger receptor class B type I promotes atherosclerotic lesion development in apolipoprotein E-deficient mice. Circulation. 2003 Nov 4;108(18):2258–2263. doi: 10.1161/01.CIR.0000093189.97429.9D
  • Yin Q, Chang H, Shen Q, et al. Photobiomodulation therapy promotes the ATP-binding cassette transporter A1-dependent cholesterol efflux in macrophage to ameliorate atherosclerosis. J Cell Mol Med. 2021 Jun;25(11):5238–5249. doi: 10.1111/jcmm.16531
  • Chaves LD, Abyad S, Honan AM, et al. Unconjugated p-cresol activates macrophage macropinocytosis leading to increased LDL uptake. JCI Insight. 2021 Jun 8;6(11). doi: 10.1172/jci.insight.144410
  • Chistiakov DA, Melnichenko AA, Myasoedova VA, et al. Mechanisms of foam cell formation in atherosclerosis. J Mol Med (Berl). 2017 Nov;95(11):1153–1165. doi: 10.1007/s00109-017-1575-8
  • Yamamoto S. Molecular mechanisms underlying uremic toxin-related systemic disorders in chronic kidney disease: focused on beta(2)-microglobulin-related amyloidosis and indoxyl sulfate-induced atherosclerosis-Oshima award address 2016. Clin Exp Nephrol. 2019 Feb;23(2):151–157. doi: 10.1007/s10157-018-1588-9
  • Du Y, Li X, Su C, et al. Butyrate protects against high-fat diet-induced atherosclerosis via up-regulating ABCA1 expression in apolipoprotein E-deficiency mice. Br J Pharmacol. 2020 Apr;177(8):1754–1772. doi: 10.1111/bph.14933
  • Geng J, Yang C, Wang B, et al. Trimethylamine N-oxide promotes atherosclerosis via CD36-dependent MAPK/JNK pathway. Biomed Pharmacother. 2018 Jan;97:941–947.
  • Wu P, Chen J, Chen J, et al. Trimethylamine N-oxide promotes apoE(-/-) mice atherosclerosis by inducing vascular endothelial cell pyroptosis via the SDHB/ROS pathway. J Cell Physiol. 2020 Oct;235(10):6582–6591. doi: 10.1002/jcp.29518
  • O’Morain VL, Chen J, Plummer SF, et al. Anti-atherogenic actions of the Lab4b consortium of probiotics in vitro. Int J Mol Sci. 2023 Feb 11;24(4):3639. doi: 10.3390/ijms24043639
  • Sacher S, Mukherjee A, Ray A. Deciphering structural aspects of reverse cholesterol transport: mapping the knowns and unknowns. Biol Rev Camb Philos Soc. 2023 Mar 7;98(4):1160–1183. doi: 10.1111/brv.12948
  • Jebari-Benslaiman S, Uribe KB, Benito-Vicente A, et al. Boosting cholesterol efflux from foam cells by sequential administration of rHDL to deliver MicroRNA and to remove cholesterol in a Triple-cell 2D atherosclerosis model. Small. 2022 Apr;18(13):e2105915. doi: 10.1002/smll.202105915
  • Robichaud S, Rasheed A, Pietrangelo A, et al. Autophagy is differentially regulated in leukocyte and nonleukocyte foam cells during atherosclerosis. Circ Res. 2022 Mar 18;130(6):831–847. doi: 10.1161/CIRCRESAHA.121.320047
  • Javadifar A, Rastgoo S, Banach M, et al. Foam cells as therapeutic targets in atherosclerosis with a focus on the regulatory roles of non-coding RNAs. Int J Mol Sci. 2021 Mar 3;22(5):2529. doi: 10.3390/ijms22052529
  • Xu S, Kamato D, Little PJ, et al. Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics. Pharmacol Ther. 2019 Apr;196:15–43.
  • Dai Y, Wu X, Dai D, et al. MicroRNA-98 regulates foam cell formation and lipid accumulation through repression of LOX-1. Redox Biol. 2018 Jun;16:255–262.
  • Chen W, Liu Y, Li L, et al. The potential role and mechanism of circRnas in foam cell formation. Noncoding RNA Res. 2023 Sep;8(3):315–325. doi: 10.1016/j.ncrna.2023.03.005
  • Afonso MS, Sharma M, Schlegel M, et al. miR-33 silencing reprograms the immune cell landscape in atherosclerotic plaques. Circ Res. 2021 Apr 16;128(8):1122–1138. doi: 10.1161/CIRCRESAHA.120.317914
  • Rotllan N, Ramirez CM, Aryal B, et al. Therapeutic silencing of microRNA-33 inhibits the progression of atherosclerosis in Ldlr-/- mice–brief report. Arterioscler Thromb Vasc Biol. 2013 Aug;33(8):1973–1977. doi: 10.1161/ATVBAHA.113.301732
  • Rayner KJ, Esau CC, Hussain FN, et al. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature. 2011 Oct 19;478(7369):404–407. doi: 10.1038/nature10486
  • Yuan C, Liu L, Tayier B, et al. Experimental study on the optimization of ANM33 release in foam cells. Open Life Sci. 2023;18(1):20220564. doi: 10.1515/biol-2022-0564
  • Zhang X, Rotllan N, Canfran-Duque A, et al. Targeted suppression of miRNA-33 using pHLIP Improves atherosclerosis regression. Circ Res. 2022 Jun 24;131(1):77–90. doi: 10.1161/CIRCRESAHA.121.320296
  • Jiang T, Xu L, Zhao M, et al. Dual targeted delivery of statins and nucleic acids by chitosan-based nanoparticles for enhanced antiatherosclerotic efficacy. Biomaterials. 2022 Jan;280:121324.
  • Price NL, Goedeke L, Suarez Y, et al. miR-33 in cardiometabolic diseases: lessons learned from novel animal models and approaches. EMBO Mol Med. 2021 May 7;13(5):e12606. doi: 10.15252/emmm.202012606
  • Soumya RS, Raghu KG. Recent advances on nanoparticle-based therapies for cardiovascular diseases. J Cardiol. 2023 Jan;81(1):10–18. doi: 10.1016/j.jjcc.2022.02.009
  • Devlin CM, Leventhal AR, Kuriakose G, et al. Acid sphingomyelinase promotes lipoprotein retention within early atheromata and accelerates lesion progression. Arterioscler Thromb Vasc Biol. 2008 Oct;28(10):1723–1730. doi: 10.1161/ATVBAHA.108.173344
  • Tabas I, Williams KJ, Boren J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation. 2007 Oct 16;116(16):1832–1844. doi: 10.1161/CIRCULATIONAHA.106.676890
  • Zhao M, You B, Wang X, et al. Desipramine enhances the stability of atherosclerotic plaque in rabbits monitored with molecular imaging. PLoS One. 2023;18(3):e0283612. doi: 10.1371/journal.pone.0283612
  • Navab M, Anantharamaiah GM, Reddy ST, et al. An oral apoJ peptide renders HDL antiinflammatory in mice and monkeys and dramatically reduces atherosclerosis in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1932–1937. doi: 10.1161/01.ATV.0000174589.70190.e2
  • Rivas-Urbina A, Rull A, Aldana-Ramos J, et al. Subcutaneous administration of apolipoprotein J-Derived mimetic peptide d-[113–122]apoJ improves LDL and HDL function and prevents atherosclerosis in LDLR-KO mice. Biomolecules. 2020 May 29;10(6):829. doi: 10.3390/biom10060829
  • Nguyen SD, Javanainen M, Rissanen S, et al. Apolipoprotein A-I mimetic peptide 4F blocks sphingomyelinase-induced LDL aggregation. J Lipid Res. 2015 Jun;56(6):1206–1221. doi: 10.1194/jlr.M059485
  • Wen Y, Ahmad F, Mohri Z, et al. Cysteamine inhibits lysosomal oxidation of low density lipoprotein in human macrophages and reduces atherosclerosis in mice. Atherosclerosis. 2019 Dec;291:9–18.
  • Haka AS, Grosheva I, Chiang E, et al. Macrophages create an acidic extracellular hydrolytic compartment to digest aggregated lipoproteins. Mol Biol Cell. 2009 Dec;20(23):4932–4940. doi: 10.1091/mbc.e09-07-0559
  • Maxfield FR, Barbosa-Lorenzi VC, Singh RK. Digestive exophagy: phagocyte digestion of objects too large for phagocytosis. Traffic. 2020 Jan;21(1):6–12. doi: 10.1111/tra.12712
  • Lehti S, Nguyen SD, Belevich I, et al. Extracellular Lipids Accumulate in Human Carotid Arteries as Distinct Three-Dimensional Structures and Have Proinflammatory Properties. Am J Pathol. 2018 Feb;188(2):525–538. doi: 10.1016/j.ajpath.2017.09.019
  • Oorni K, Kovanen PT. Aggregation susceptibility of low-density lipoproteins—A novel modifiable biomarker of cardiovascular risk. J Clin Med. 2021 Apr 19;10(8):1769. doi: 10.3390/jcm10081769
  • Duewell P, Kono H, Rayner KJ, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010 Apr 29;464(7293):1357–1361. doi: 10.1038/nature08938
  • Singh RK, Lund FW, Haka AS, et al. High-density lipoprotein or cyclodextrin extraction of cholesterol from aggregated LDL reduces foam cell formation. J Cell Sci. 2019 Dec 2;132(23). doi: 10.1242/jcs.237271
  • Kim H, Han J, Park JH. Cyclodextrin polymer improves atherosclerosis therapy and reduces ototoxicity. J Control Release. 2020 Mar 10;319:77–86. doi: 10.1016/j.jconrel.2019.12.021
  • Zimmer S, Grebe A, Bakke SS, et al. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming. Sci Transl Med. 2016 Apr 6;8(333):333ra50. doi: 10.1126/scitranslmed.aad6100
  • Evans TD, Jeong SJ, Zhang X, et al. TFEB and trehalose drive the macrophage autophagy-lysosome system to protect against atherosclerosis. Autophagy. 2018;14(4):724–726. doi: 10.1080/15548627.2018.1434373
  • Grootaert MO, da Costa Martins PA, Bitsch N, et al. Defective autophagy in vascular smooth muscle cells accelerates senescence and promotes neointima formation and atherogenesis. Autophagy. 2015 Nov 2;11(11):2014–2032. doi: 10.1080/15548627.2015.1096485
  • Liao X, Sluimer JC, Wang Y, et al. Macrophage autophagy plays a protective role in advanced atherosclerosis. Cell Metab. 2012 Apr 4;15(4):545–553. doi: 10.1016/j.cmet.2012.01.022
  • Masuyama A, Mita T, Azuma K, et al. Defective autophagy in vascular smooth muscle cells enhances atherosclerotic plaque instability. Biochem Biophys Res Commun. 2018 Nov 10;505(4):1141–1147. doi: 10.1016/j.bbrc.2018.09.192
  • Osonoi Y, Mita T, Azuma K, et al. Defective autophagy in vascular smooth muscle cells enhances cell death and atherosclerosis. Autophagy. 2018;14(11):1991–2006. doi: 10.1080/15548627.2018.1501132
  • Peng R, Ji H, Jin L, et al. Macrophage-based therapies for atherosclerosis management. J Immunol Res. 2020;2020:8131754. doi: 10.1155/2020/8131754
  • Liu X, Tang Y, Cui Y, et al. Autophagy is associated with cell fate in the process of macrophage-derived foam cells formation and progress. J Biomed Sci. 2016 Jul 30;23(1):57. doi: 10.1186/s12929-016-0274-z
  • Bruiners N, Dutta NK, Guerrini V, et al. The anti-tubercular activity of simvastatin is mediated by cholesterol-driven autophagy via the AMPK-mTORC1-TFEB axis. J Lipid Res. 2020 Dec;61(12):1617–1628. doi: 10.1194/jlr.RA120000895
  • Xing L, Zhou X, Li AH, et al. Atheroprotective effects and molecular mechanism of Berberine. Front Mol Biosci. 2021;8:762673. doi: 10.3389/fmolb.2021.762673
  • Leng S, Iwanowycz S, Saaoud F, et al. Ursolic acid enhances macrophage autophagy and attenuates atherogenesis. J Lipid Res. 2016 Jun;57(6):1006–1016. doi: 10.1194/jlr.M065888
  • Martinet W, Verheye S, De Meyer GR. Everolimus-induced mTOR inhibition selectively depletes macrophages in atherosclerotic plaques by autophagy. Autophagy. 2007 May;3(3):241–244. doi: 10.4161/auto.3711
  • Verheye S, Martinet W, Kockx MM, et al. Selective clearance of macrophages in atherosclerotic plaques by autophagy. J Am Coll Cardiol. 2007 Feb 13;49(6):706–715. doi: 10.1016/j.jacc.2006.09.047
  • Martinet W, De Loof H, De Meyer GRY. mTOR inhibition: a promising strategy for stabilization of atherosclerotic plaques. Atherosclerosis. 2014 Apr;233(2):601–607. doi: 10.1016/j.atherosclerosis.2014.01.040
  • Zhang Y, Cao X, Zhu W, et al. Resveratrol enhances autophagic flux and promotes ox-LDL degradation in HUVECs via upregulation of SIRT1. Oxid Med Cell Longev. 2016;2016:7589813. doi: 10.1155/2016/7589813
  • Ouimet M, Ediriweera H, Afonso MS, et al. microRNA-33 Regulates Macrophage Autophagy in Atherosclerosis. Arterioscler Thromb Vasc Biol. 2017 Jun;37(6):1058–1067. doi: 10.1161/ATVBAHA.116.308916
  • Liu B, Zhang B, Guo R, et al. Enhancement in efferocytosis of oxidized low-density lipoprotein-induced apoptotic RAW264.7 cells through Sirt1-mediated autophagy. Int J Mol Med. 2014 Mar;33(3):523–533. doi: 10.3892/ijmm.2013.1609
  • Martinez J, Almendinger J, Oberst A, et al. Microtubule-associated protein 1 light chain 3 alpha (LC3)-associated phagocytosis is required for the efficient clearance of dead cells. Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):17396–17401. doi: 10.1073/pnas.1113421108
  • Razani B, Feng C, Coleman T, et al. Autophagy links inflammasomes to atherosclerotic progression. Cell Metab. 2012 Apr 4;15(4):534–544. doi: 10.1016/j.cmet.2012.02.011
  • Zeng C, Wang R, Tan H. Role of Pyroptosis in Cardiovascular Diseases and its Therapeutic Implications. Int J Biol Sci. 2019;15(7):1345–1357. doi: 10.7150/ijbs.33568
  • Liu Y, Levine B. Autosis and autophagic cell death: the dark side of autophagy. Cell Death Differ. 2015 Mar;22(3):367–376. doi: 10.1038/cdd.2014.143
  • Martinet W, Coornaert I, Puylaert P, et al. Macrophage death as a pharmacological target in atherosclerosis. Front Pharmacol. 2019;10:306. doi: 10.3389/fphar.2019.00306
  • Martinet W, Verheye S, De Meyer I, et al. Everolimus triggers cytokine release by macrophages: rationale for stents eluting everolimus and a glucocorticoid. Arterioscler Thromb Vasc Biol. 2012 May;32(5):1228–1235. doi: 10.1161/ATVBAHA.112.245381
  • Ko JH, Yoon SO, Lee HJ, et al. Rapamycin regulates macrophage activation by inhibiting NLRP3 inflammasome-p38 MAPK-NFkappaB pathways in autophagy- and p62-dependent manners. Oncotarget. 2017 Jun 20;8(25):40817–40831. doi: 10.18632/oncotarget.17256
  • Martinet W, Verheye S, De Meyer GR. Selective depletion of macrophages in atherosclerotic plaques via macrophage-specific initiation of cell death. Trends Cardiovasc Med. 2007 Feb;17(2):69–75. doi: 10.1016/j.tcm.2006.12.004
  • Wang X, Li L, Li M, et al. Knockdown of mTOR by lentivirus‑mediated RNA interference suppresses atherosclerosis and stabilizes plaques via a decrease of macrophages by autophagy in apolipoprotein E‑deficient mice. Int J Mol Med. 2013 Nov;32(5):1215–1221. doi: 10.3892/ijmm.2013.1494
  • Zhai C, Cheng J, Mujahid H, et al. Selective inhibition of PI3K/Akt/mTOR signaling pathway regulates autophagy of macrophage and vulnerability of atherosclerotic plaque. PLoS One. 2014;9(3):e90563. doi: 10.1371/journal.pone.0090563
  • De Meyer GR, Grootaert MO, Michiels CF, et al. Autophagy in vascular disease. Circ Res. 2015 Jan 30;116(3):468–479. doi: 10.1161/CIRCRESAHA.116.303804
  • Sergin I, Evans TD, Zhang X, et al. Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis. Nat Commun. 2017 Jun 7;8(1):15750. doi: 10.1038/ncomms15750
  • Jeong SJ, Stitham J, Evans TD, et al. Trehalose causes low-grade lysosomal stress to activate TFEB and the autophagy-lysosome biogenesis response. Autophagy. 2021 Nov;17(11):3740–3752. doi: 10.1080/15548627.2021.1896906
  • Lazaro I, Lopez-Sanz L, Bernal S, et al. Nrf2 activation provides atheroprotection in diabetic mice through concerted upregulation of antioxidant, anti-inflammatory, and autophagy mechanisms. Front Pharmacol. 2018;9:819. doi: 10.3389/fphar.2018.00819
  • Martinet W, Schrijvers DM, De Meyer GR. Necrotic cell death in atherosclerosis. Basic Res Cardiol. 2011 Sep;106(5):749–760. doi: 10.1007/s00395-011-0192-x
  • Mallat Z, Hugel B, Ohan J, et al. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. Circulation. 1999 Jan 26;99(3):348–353. doi: 10.1161/01.CIR.99.3.348
  • Kolodgie FD, Narula J, Burke AP, et al. Localization of apoptotic macrophages at the site of plaque rupture in sudden coronary death. Am J Pathol. 2000 Oct;157(4):1259–1268. doi: 10.1016/S0002-9440(10)64641-X
  • Liu J, Thewke DP, Su YR, et al. Reduced macrophage apoptosis is associated with accelerated atherosclerosis in low-density lipoprotein receptor-null mice. Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):174–179. doi: 10.1161/01.ATV.0000148548.47755.22
  • Thorp E, Li Y, Bao L, et al. Brief report: increased apoptosis in advanced atherosclerotic lesions of Apoe-/- mice lacking macrophage Bcl-2. Arterioscler Thromb Vasc Biol. 2009 Feb;29(2):169–172. doi: 10.1161/ATVBAHA.108.176495
  • Xu F, Yao F, Ning Y. MicroRNA-202-5p-dependent inhibition of Bcl-2 contributes to macrophage apoptosis and atherosclerotic plaque formation. Gene. 2023 May 30;867:147366. doi: 10.1016/j.gene.2023.147366
  • Arai S, Shelton JM, Chen M, et al. A role for the apoptosis inhibitory factor AIM/Spalpha/Api6 in atherosclerosis development. Cell Metab. 2005 Mar;1(3):201–213. doi: 10.1016/j.cmet.2005.02.002
  • Majno G, Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol. 1995 Jan;146(1):3–15.
  • Henson PM, Bratton DL, Fadok VA. Apoptotic cell removal. Curr Biol. 2001 Oct 2;11(19):R795–805. doi: 10.1016/S0960-9822(01)00474-2
  • Leeper NJ. The role of necroptosis in atherosclerotic disease. JACC Basic Transl Sci. 2016 Oct;1(6):548–550. doi: 10.1016/j.jacbts.2016.08.002
  • Karunakaran D, Nguyen MA, Geoffrion M, et al. RIPK1 expression associates with inflammation in early atherosclerosis in humans and can be therapeutically silenced to reduce NF-kappaB activation and atherogenesis in mice. Circulation. 2021 Jan 12;143(2):163–177. doi: 10.1161/CIRCULATIONAHA.118.038379
  • Degterev A, Huang Z, Boyce M, et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol. 2005 Jul;1(2):112–119. doi: 10.1038/nchembio711
  • Karunakaran D, Geoffrion M, Wei L, et al. Targeting macrophage necroptosis for therapeutic and diagnostic interventions in atherosclerosis. Sci Adv. 2016 Jul;2(7):e1600224. doi: 10.1126/sciadv.1600224
  • Hu G, Yuan Z, Wang J. Autophagy inhibition and ferroptosis activation during atherosclerosis: hypoxia-inducible factor 1alpha inhibitor PX-478 alleviates atherosclerosis by inducing autophagy and suppressing ferroptosis in macrophages. Biomed Pharmacother. 2023 May;161:114333. doi: 10.1016/j.biopha.2023.114333
  • van der Heijden, T, Kritikou E, Venema W, et al. NLRP3 Inflammasome Inhibition by MCC950 Reduces Atherosclerotic Lesion Development in Apolipoprotein E–Deficient Mice—Brief Report. Arterioscler Thromb Vasc Biol. 2017 Aug;37(8):1457–1461. doi: 10.1161/ATVBAHA.117.309575
  • Zeng W, Wu D, Sun Y, et al. The selective NLRP3 inhibitor MCC950 hinders atherosclerosis development by attenuating inflammation and pyroptosis in macrophages. Sci Rep. 2021 Sep 29;11(1):19305. doi: 10.1038/s41598-021-98437-3
  • Sharma A, Choi JSY, Stefanovic N, et al. Specific NLRP3 inhibition protects against diabetes-associated atherosclerosis. Diabetes. 2021 Mar;70(3):772–787. doi: 10.2337/db20-0357
  • Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with Canakinumab for atherosclerotic disease. N Engl J Med. 2017 Sep 21;377(12):1119–1131. doi: 10.1056/NEJMoa1707914
  • Oumouna-Benachour K, Hans CP, Suzuki Y, et al. Poly(ADP-ribose) polymerase inhibition reduces atherosclerotic plaque size and promotes factors of plaque stability in apolipoprotein E-deficient mice: effects on macrophage recruitment, nuclear factor-kappaB nuclear translocation, and foam cell death. Circulation. 2007 May 8;115(18):2442–2450. doi: 10.1161/CIRCULATIONAHA.106.668756
  • Xie JJ, Yu X, Liao YH, et al. Poly (ADP-Ribose) polymerase inhibition attenuates atherosclerotic plaque development in ApoE-/- mice with hyperhomocysteinemia. J Atheroscler Thromb. 2009 Oct;16(5):641–653. doi: 10.5551/jat.1586
  • Gough PJ, Wille PT, Raines EW, et al. Macrophage expression of active MMP-9 induces acute plaque disruption in apoE-deficient mice. J Clin Invest. 2006 Jan;116(1):59–69. doi: 10.1172/JCI25074
  • Virmani R, Burke AP, Kolodgie FD, et al. Vulnerable plaque: the pathology of unstable coronary lesions. J Interv Cardiol. 2002 Dec;15(6):439–446. doi: 10.1111/j.1540-8183.2002.tb01087.x
  • Chinetti-Gbaguidi G, Colin S, Staels B. Macrophage subsets in atherosclerosis. Nat Rev Cardiol. 2015 Jan;12(1):10–17. doi: 10.1038/nrcardio.2014.173
  • Kojima Y, Weissman IL, Leeper NJ. The role of efferocytosis in atherosclerosis. Circulation. 2017 Jan 31;135(5):476–489. doi: 10.1161/CIRCULATIONAHA.116.025684
  • Tao H, Yancey PG, Babaev VR, et al. Macrophage SR-BI mediates efferocytosis via src/PI3K/Rac1 signaling and reduces atherosclerotic lesion necrosis. J Lipid Res. 2015 Aug;56(8):1449–1460. doi: 10.1194/jlr.M056689
  • Kojima Y, Volkmer JP, McKenna K, et al. CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis. Nature. 2016 Aug 4;536(7614):86–90. doi: 10.1038/nature18935
  • Farahi L, Sinha SK, Lusis AJ. Roles of macrophages in atherogenesis. Front Pharmacol. 2021;12:785220. doi: 10.3389/fphar.2021.785220
  • Sanchez-Gaytan BL, Fay F, Lobatto ME, et al. HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages. Bioconjug Chem. 2015 Mar 18;26(3):443–451. doi: 10.1021/bc500517k
  • Childs BG, Baker DJ, Wijshake T, et al. Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science. 2016 Oct 28;354(6311):472–477. doi: 10.1126/science.aaf6659
  • Wang S, Yang S, Chen Y, et al. Ginsenoside Rb2 alleviated atherosclerosis by inhibiting M1 macrophages polarization induced by MicroRNA-216a. Front Pharmacol. 2021;12:764130. doi: 10.3389/fphar.2021.764130
  • Daemen S, Gainullina A, Kalugotla G, et al. Dynamic shifts in the composition of resident and recruited macrophages influence tissue remodeling in NASH. Cell Rep. 2021 Jan 12;34(2):108626. doi: 10.1016/j.celrep.2020.108626
  • Nishida M, Miyagawa J, Yamashita S, et al. Localization of CD9, an enhancer protein for proheparin-binding epidermal growth factor-like growth factor, in human atherosclerotic plaques: possible involvement of juxtacrine growth mechanism on smooth muscle cell proliferation. Arterioscler Thromb Vasc Biol. 2000 May;20(5):1236–1243. doi: 10.1161/01.ATV.20.5.1236
  • Cho JH, Kim EC, Son Y, et al. CD9 induces cellular senescence and aggravates atherosclerotic plaque formation. Cell Death Differ. 2020 Sep;27(9):2681–2696. doi: 10.1038/s41418-020-0537-9
  • Kale A, Sharma A, Stolzing A, et al. Role of immune cells in the removal of deleterious senescent cells. Immun Ageing. 2020;17(1):16. doi: 10.1186/s12979-020-00187-9
  • Arora S, Thompson PJ, Wang Y, et al. Invariant natural killer T cells coordinate removal of senescent cells. Med. 2021 Aug 13;2(8):938–950. doi: 10.1016/j.medj.2021.04.014
  • Laffont B, Rayner KJ. MicroRNAs in the pathobiology and therapy of atherosclerosis. Can J Cardiol. 2017 Mar;33(3):313–324. doi: 10.1016/j.cjca.2017.01.001
  • Schober A, Weber C. Mechanisms of MicroRNAs in atherosclerosis. Annu Rev Pathol. 2016 May 23;11(1):583–616. doi: 10.1146/annurev-pathol-012615-044135
  • Li Z, Zhao Y, Suguro S, et al. MicroRNAs regulate function in atherosclerosis and clinical implications. Oxid Med Cell Longev. 2023;2023:2561509. doi: 10.1155/2023/2561509
  • Wang C, Yang W, Liang X, et al. MicroRNA-761 modulates foam cell formation and inflammation through autophagy in the progression of atherosclerosis. Mol Cell Biochem. 2020 Nov;474(1–2):135–146. doi: 10.1007/s11010-020-03839-y
  • Cho JR, Lee CY, Lee J, et al. MicroRNA-761 inhibits angiotensin II-induced vascular smooth muscle cell proliferation and migration by targeting mammalian target of rapamycin. Clin Hemorheol Microcirc. 2015 Sep 25;63(1):45–56. doi: 10.3233/CH-151981
  • Long B, Wang K, Li N, et al. miR-761 regulates the mitochondrial network by targeting mitochondrial fission factor. Free Radic Biol Med. 2013 Dec;65:371–379.
  • Minniti ME, Pedrelli M, Vedin LL, et al. Insights from liver-humanized mice on cholesterol lipoprotein metabolism and LXR-Agonist pharmacodynamics in humans. Hepatology. 2020 Aug;72(2):656–670. doi: 10.1002/hep.31052
  • Zhao Y, Qu H, Wang Y, et al. Small rodent models of atherosclerosis. Biomed Pharmacother. 2020 Sep;129:110426.
  • Wang Y, Dubland JA, Allahverdian S, et al. Smooth muscle cells contribute the majority of foam cells in ApoE (apolipoprotein E)-deficient mouse atherosclerosis. Arterioscler Thromb Vasc Biol. 2019 May;39(5):876–887. doi: 10.1161/ATVBAHA.119.312434
  • Cochain C, Vafadarnejad E, Arampatzi P, et al. Single-cell RNA-Seq reveals the transcriptional landscape and heterogeneity of aortic macrophages in murine atherosclerosis. Circ Res. 2018 Jun 8;122(12):1661–1674. doi: 10.1161/CIRCRESAHA.117.312509
  • Ouyang Z, Zhong J, Shen J, et al. The cell origins of foam cell and lipid metabolism regulated by mechanical stress in atherosclerosis. Front Physiol. 2023;14:1179828. doi: 10.3389/fphys.2023.1179828

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