Cardiovascular and cerebrovascular diseases, such as coronary heart disease and stroke, caused by atherosclerosis have become the “number one killer”, seriously endangering human health in developing and developed countries. Atherosclerosis mainly occurs in large and medium-sized arteries and involves intimal thickening, accumulation of foam cells, and formation of atheromatous plaques. Autophagy is a cellular catabolic process that has evolved to defend cells from the turnover of intracellular molecules. Autophagy is thought to play an important role in the development of plaques. This review focuses on studies on autophagy in cells involved in the formation of atherosclerotic plaques, such as monocytes, macrophages, endothelial cells, dendritic cells, and vascular smooth muscle cells, indicating that autophagy plays an important role in plaque development. We mainly discuss the roles of autophagy in these cells in maintaining the stability of atherosclerotic plaques, providing a reference for the next steps to unravel the mechanisms of atherogenesis.
KobiyamaKLeyK.Atherosclerosis: a chronic inflammatory disease with an autoimmune component. Circ Res2018;
123:1118–20
2.
ZhaoDLiuJWangMZhangXZhouM.Epidemiology of cardiovascular disease in China: current features and implications. Nat Rev Cardiol2019;
16:203–12
3.
Emini VeseliBPerrottaPDe MeyerGRARothLVan der DoncktCMartinetWDe MeyerGRY.Animal models of atherosclerosis. Eur J Pharmacol2017;
816:3–13
4.
ManggeHAlmerG.Immune-Mediated inflammation in vulnerable atherosclerotic plaques. Molecules2019;
24:3072
5.
LiuHCaoYTongTShiJZhangYYangYLiuC.Autophagy in atherosclerosis: a phenomenon found in human carotid atherosclerotic plaques. Chin Med J (Engl)2015;
128:69–74
6.
TomaipitincaMMancinelliGPetrungaroMFacchianoZGaudioG.The role of autophagy in liver epithelial cells and its impact on systemic homeostasis. Nutrients2019;
11:827
7.
MizushimaN.A brief history of autophagy from cell biology to physiology and disease. Nat Cell Biol2018;
20:521–7
8.
ParzychKRKlionskyDJ.An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal2014;
20:460–73
9.
MiaoJZangXCuiXZhangJ.Autophagy, hyperlipidemia, and atherosclerosis. Adv Exp Med Biol2020;
1207:237–64
10.
MartinetWDe MeyerGRY.Autophagy in atherosclerosis: a cell survival and death phenomenon with therapeutic potential. Circ Res2009;
104:304–17
Mialet-PerezJVindisC.Autophagy in health and disease: focus on the cardiovascular system. Essays Biochem2017;
61:721–32
13.
KeXHuangYLiLXinFXuLZhangYZengZLinFSongY.Berberine attenuates arterial plaque formation in atherosclerotic rats with Damp-Heat syndrome via regulating autophagy. Drug Des Devel Ther2020;
14:2449–60
14.
VergalloRCreaF.Atherosclerotic plaque healing. N Engl J Med2020;
383:846–57
15.
GrootaertMOJRothLSchrijversDMDe MeyerGRYMartinetW.Defective autophagy in atherosclerosis: to die or to senesce?Oxid Med Cell Longev2018;
2018:7687083
16.
MunjalAKhandiaR.Atherosclerosis: orchestrating cells and biomolecules involved in its activation and inhibition. Adv Protein Chem Struct Biol2020;
120:85–122
GuoF-XWuQLiPZhengLYeSDaiX-YKangC-MLuJ-BXuB-MXuY-JXiaoLLuZ-FBaiH-LHuY-WWangQ.The role of the LncRNA-FA2H-2-MLKL pathway in atherosclerosis by regulation of autophagy flux and inflammation through mTOR-dependent signaling. Cell Death Differ2019;
26:1670–87
23.
YauJWSinghKKHouYLeiXRamadanAQuanATeohHKueblerWMAl-OmranMYanagawaBNiHVermaS.Endothelial-specific deletion of autophagy-related 7 (ATG7) attenuates arterial thrombosis in mice. J Thorac Cardiovasc Surg2017;
154:978–88.e1
24.
MasuyamaAMitaTAzumaKOsonoiYNakajimaKGotoHNishidaYMiyatsukaTMitsumataMWatadaH.Defective autophagy in vascular smooth muscle cells enhances atherosclerotic plaque instability. Biochem Biophys Res Commun2018;
505:1141–7
25.
PerrottaI.The use of electron microscopy for the detection of autophagy in human atherosclerosis. Micron2013;
50:7–13
26.
KratofilRMKubesPDenisetJF.Monocyte conversion during inflammation and injury. Arterioscler Thromb Vasc Biol2017;
37:35–42
27.
BadimonLStoreyRVilahurG.Update on lipids, inflammation and atherothrombosis. Thromb Haemost2011;
105:S34–42
28.
GhattasAGriffithsHRDevittALipGYHShantsilaE.Monocytes in coronary artery disease and atherosclerosis. J Am Coll Cardiol2013;
62:1541–51
29.
XuH-DQinZ-H.Beclin 1, bcl-2 and autophagy. Adv Exp Med Biol2019;
1206:109–26
30.
ZhaoKXuXSMengXLiYLLiJFChenWQ.Autophagy of monocytes attenuates the vulnerability of coronary atherosclerotic plaques. Coron Artery Dis2013;
24:651–6
31.
SchrijversDDemeyerGHermanAMartinetW.Phagocytosis in atherosclerosis: Molecular mechanisms and implications for plaque progression and stability. Cardiovasc Res2007;
73:470–80
32.
ZhangMZhuHDingYLiuZCaiZZouM-H.AMP-activated protein kinase α1 promotes atherogenesis by increasing monocyte-to-macrophage differentiation. J Biol Chem2017;
292:7888–903
33.
JiaSJGaoKQZhaoM.Epigenetic regulation in monocyte/macrophage: a key player during atherosclerosis. Cardiovasc Ther2017;
35:e12262
34.
MooreKJSheedyFJFisherEA.Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol2013;
13:709–21
35.
ZhaiCChengJMujahidHWangHKongJYinYLiJZhangYJiXChenW.Selective inhibition of PI3K/akt/mTOR signaling pathway regulates autophagy of macrophage and vulnerability of atherosclerotic plaque. PLoS One2014;
9:e90563
36.
LiaoXSluimerJCWangYSubramanianMBrownKPattisonJSRobbinsJMartinezJTabasI.Macrophage autophagy plays a protective role in advanced atherosclerosis. Cell Metab2012;
15:545–53
37.
OuimetMFranklinVMakELiaoXTabasIMarcelYL.Autophagy regulates cholesterol efflux from macrophage foam cells via lysosomal acid lipase. Cell Metab2011;
13:655–67
38.
ShaoBHanBZengYSuDLiuC.The roles of macrophage autophagy in atherosclerosis. Acta Pharmacol Sin2016;
37:150–6
39.
BasatemurGLJørgensenHFClarkeMCHBennettMRMallatZ.Vascular smooth muscle cells in atherosclerosis. Nat Rev Cardiol2019;
16:727–44
40.
SchrijversDMDe MeyerGRYMartinetW.Autophagy in atherosclerosis: a potential drug target for plaque stabilization. Arterioscler Thromb Vasc Biol2011;
31:2787–91
41.
TimmKNTylerDJ.The role of AMPK activation for cardioprotection in doxorubicin-Induced cardiotoxicity. Cardiovasc Drugs Ther2020;
34:255–69
42.
OuHLiuCFengWXiaoXTangSMoZ.Role of AMPK in atherosclerosis via autophagy regulation. Sci China Life Sci2018;
61:1212–21
TheodorouKBoonRA.Endothelial cell metabolism in atherosclerosis. Front Cell Dev Biol2018;
6:82
47.
ZhangY-YShiY-NZhuNWangWDengC-FXieX-JLiaoD-FQinL.Autophagy: a killer or guardian of vascular smooth muscle cells. J Drug Target2020;
28:449–55
48.
BharathLPMuellerRLiYRuanTKunzDGoodrichRMillsTDeeterLSargsyanAAnandh BabuPVGrahamTESymonsJD.Impairment of autophagy in endothelial cells prevents shear-stress-induced increases in nitric oxide bioavailability. Can J Physiol Pharmacol2014;
92:605–12
49.
SakamotoKNagamatsuSYamamotoEKaikitaKTsujitaK.Atherosclerotic coronary plaque development visualized by in vivo coronary imaging. Circ J2018;
82:1727–34
50.
ZhangXRamírezCMAryalBMadrigal-MatuteJLiuXDiazATorrecilla-ParraMSuárezYCuervoAMSessaWCFernández-HernandoC.Cav-1 (caveolin-1) deficiency increases autophagy in the endothelium and attenuates vascular inflammation and atherosclerosis. Arterioscler Thromb Vasc Biol2020;
40:1510–22
51.
SantovitoDEgeaVBidzhekovKNatarelliLMourãoABlanchetXWichapongKAslaniMBrunßenCHorckmansMHristovMGeerlofALutgensEDaemenMJAPHackengTRiesCChavakisTMorawietzHNaumannRvon HundelshausenPSteffensSDuchêneJMegensRTASattlerMWeberC.Noncanonical inhibition of caspase-3 by a nuclear microRNA confers endothelial protection by autophagy in atherosclerosis. Sci Transl Med2020;
12:eaaz2294
52.
TurpaevKT.Transcription factor KLF2 and its role in the regulation of inflammatory processes. Biochemistry Moscow2020;
85:54–67
53.
BobryshevYV.Dendritic cells and their role in atherogenesis. Lab Invest2010;
90:970–84
54.
GhislatGLawrenceT.Autophagy in dendritic cells. Cell Mol Immunol2018;
15:944–52
55.
BobryshevY.Mapping of vascular dendritic cells in atherosclerotic arteries suggests their involvement in local immune-inflammatory reactions. Cardiovasc Res1998;
37:799–810
56.
MillonigGNiedereggerHRablWHochleitnerBWHoeferDRomaniNWickG.Network of vascular-associated dendritic cells in intima of healthy young individuals. Arterioscler Thromb Vasc Biol2001;
21:503–8
57.
YilmazALochnoMTraegFCichaIReissCStumpfCRaazDAngerTAmannKProbstTLudwigJDanielWGGarlichsCD.Emergence of dendritic cells in rupture-prone regions of vulnerable carotid plaques. Atherosclerosis2004;
176:101–10
58.
MinternJDMacriCChinWJPanozzaSESeguraEPattersonNLZellerPBourgesDBedouiSMcMillanPJIdrisANowellCJBrownARadfordKJJohnstonAPVilladangosJA.Differential use of autophagy by primary dendritic cells specialized in cross-presentation. Autophagy2015;
11:906–17
59.
ClementMRaffortJLareyreFTsiantoulasDNewlandSLuYMastersLHarrisonJSaveljevaSMaMKLOzsvar-KozmaMLamBYHYeoGSHBinderCJKaserAMallatZ.Impaired autophagy in CD11b+ dendritic cells expands CD4+ regulatory T cells and limits atherosclerosis in mice. Circ Res2019;
125:1019–34
60.
PerrottaIAquilaS.The role of oxidative stress and autophagy in atherosclerosis. Oxid Med Cell Longev2015;
2015:130315
61.
ShanRLiuNYanYLiuB.Apoptosis, autophagy and atherosclerosis: relationships and the role of Hsp27. Pharmacol Res2021;
166:105169
62.
XuJKitadaMOguraYKoyaD.Relationship between autophagy and metabolic syndrome characteristics in the pathogenesis of atherosclerosis. Front Cell Dev Biol2021;
9:641852
