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摘要: 动脉粥样硬化是心血管疾病的重要发病原因，其患病率逐年增高，带来了庞大的经济和社会负担。近年来，人们逐渐发现M2型巨噬细胞在动脉粥样硬化病变消退的过程中扮演着重要的角色，它可以释放多种抗炎因子、促进胞葬作用和组织修复等。通过M2型巨噬细胞或可取得新的治疗进展。本文将对M2型巨噬细胞的起源与分型、极化过程及其与动脉粥样硬化病变消退之间的关系进行概述。Abstract: As the underlying etiology of cardiovascular disease, atherosclerosis takes a huge economic and social burden. Recent studies have shown that M2 macrophages play pivotal roles in the regression of atherosclerosis, including releasing multiple anti-inflammatory factors, promoting efferocytosis, and boosting tissue repair. Here we discuss the origin and identification of M2 macrophages, the signal transduction in M2 polarization, and its relationship with atherosclerosis resolution.
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Key words:
- atherosclerosis /
- macrophage polarization /
- efferocytosis
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[1] Bäck M, Yurdagul A Jr, Tabas I, et al. Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities[J]. Nat Rev Cardiol, 2019, 16(7): 389-406.
[2] Theret M, Mounier R, Rossi F. The origins and non-canonical functions of macrophages in development and regeneration[J]. Development, 2019, 146(9).
[3] Carlin LM, Stamatiades EG, Auffray C, et al. Nr4a1-dependent Ly6C(low)monocytes monitor endothelial cells and orchestrate their disposal[J]. Cell, 2013, 153(2): 362-375. doi: 10.1016/j.cell.2013.03.010
[4] Rahman K, Vengrenyuk Y, Ramsey SA, et al. Inflammatory Ly6Chi monocytes and their conversion to M2 macrophages drive atherosclerosis regression[J]. J Clin Invest, 2017, 127(8): 2904-2915. doi: 10.1172/JCI75005
[5] Mills CD. M1 and M2 Macrophages: oracles of health and disease[J]. Crit Rev Immunol, 2012, 32(6): 463-488. doi: 10.1615/CritRevImmunol.v32.i6.10
[6] Nasser MI, Zhu S, Huang H, et al. Macrophages: First guards in the prevention of cardiovascular diseases[J]. Life Sci, 2020, 250: 117559. doi: 10.1016/j.lfs.2020.117559
[7] 顾奕玥, 胡泽平, 王云飞, 等. 肝细胞生长因子活化JAK2/STAT3通路促进巨噬细胞M1型向M2型极化[J]. 安徽医科大学学报, 2019, 54(5): 696-700. doi: 10.19405/j.cnki.issn1000-1492.2019.05.006
[8] Zhang M, Nakamura K, Kageyama S, et al. Myeloid HO-1 modulates macrophage polarization and protects against ischemia-reperfusion injury[J]. JCI Insight, 2018, 3(19).
[9] Geng T, Yan Y, Xu L, et al. CD137 signaling induces macrophage M2 polarization in atherosclerosis through STAT6/PPARδ pathway[J]. Cell Signal, 2020, 72: 109628. doi: 10.1016/j.cellsig.2020.109628
[10] Ouimet M, Ediriweera HN, Gundra UM, et al. MicroRNA-33-dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis[J]. J Clin Invest, 2015, 125(12): 4334-4348. doi: 10.1172/JCI81676
[11] Qi JR, Zhao DR, Zhao L, et al. MiR-520a-3p Inhibited Macrophage Polarization and Promoted the Development of Atherosclerosis via Targeting UVRAG in Apolipoprotein E Knockout Mice[J]. Front Mol Biosci, 2020, 7: 621324.
[12] 李楠, 闫素华. 阿托伐他汀对炎症表型转化的小鼠RAW264.7细胞的保护机制研究[J/OL]. 中国医学前沿杂志(电子版), 2019, 11(10): 30-35.
[13] Chen Y, Zhang H, Hu L, et al. Pravastatin attenuates atherosclerosis after myocardial infarction by inhibiting inflammatory Ly6C(high) monocytosis in apolipoprotein E knockout mice[J]. J Int Med Res, 2020, 48(7): 1220732368.
[14] Zhang X, Qin Y, Wan X, et al. Rosuvastatin exerts anti-atherosclerotic effects by improving macrophage-related foam cell formation and polarization conversion via mediating autophagic activities[J]. J Transl Med, 2021, 19(1): 62. doi: 10.1186/s12967-021-02727-3
[15] Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions[J]. Immunity, 2010, 32(5): 593-604. doi: 10.1016/j.immuni.2010.05.007
[16] Jiménez-Garcia L, Herránz S, Luque A, et al. Critical role of p38 MAPK in IL-4-induced alternative activation of peritoneal macrophages[J]. Eur J Immunol, 2015, 45(1): 273-286. doi: 10.1002/eji.201444806
[17] Kolinko L, Shlykova O, Izmailova O, et al. SIRT1 contributes to polarization of peripheral blood monocytes by increasing STAT6 expression in young people with overweight and low-risk obesity[J]. Georgian Med News, 2021, (313): 102-112.
[18] Wang S, Cao M, Xu S, et al. Luteolin Alters Macrophage Polarization to Inhibit Inflammation[J]. Inflammation, 2020, 43(1): 95-108. doi: 10.1007/s10753-019-01099-7
[19] Oh H, Park SH, Kang MK, et al. Asaronic Acid Inhibited Glucose-Triggered M2-Phenotype Shift Through Disrupting the Formation of Coordinated Signaling of IL-4Rα-Tyk2-STAT6 and GLUT1-Akt-mTOR-AMPK[J]. Nutrients, 2020, 12(7).
[20] 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]. J Agric Food Chem, 2019, 67(3): 807-818. doi: 10.1021/acs.jafc.8b05719
[21] Arranz A, Doxaki C, Vergadi E, et al. Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization[J]. Proc Natl Acad Sci U S A, 2012, 109(24): 9517-9522. doi: 10.1073/pnas.1119038109
[22] Babaev VR, Hebron KE, Wiese CB, et al. Macrophage deficiency of Akt2 reduces atherosclerosis in Ldlr null mice[J]. J Lipid Res, 2014, 55(11): 2296-2308. doi: 10.1194/jlr.M050633
[23] Sahin E, Haubenwallner S, Kuttke M, et al. Macrophage PTEN regulates expression and secretion of arginase I modulating innate and adaptive immune responses[J]. J Immunol, 2014, 193(4): 1717-1727. doi: 10.4049/jimmunol.1302167
[24] Pauls SD, Marshall AJ. Regulation of immune cell signaling by SHIP1: A phosphatase, scaffold protein, and potential therapeutic target[J]. Eur J Immunol, 2017, 47(6): 932-945. doi: 10.1002/eji.201646795
[25] Vergadi E, Ieronymaki E, Lyroni K, et al. Akt Signaling Pathway in Macrophage Activation and M1/M2 Polarization[J]. J Immunol, 2017, 198(3): 1006-1014. doi: 10.4049/jimmunol.1601515
[26] Xie Y, Tian L, Fang Z, et al. Bushen Kangshuai tablet inhibits progression of atherosclerosis by intervening in macrophage autophagy and polarization[J]. J Tradit Chin Med, 2020, 40(1): 28-37.
[27] Lee CW, Hwang I, Park CS, et al. Macrophage heterogeneity of culprit coronary plaques in patients with acute myocardial infarction or stable angina[J]. Am J Clin Pathol, 2013, 139(3): 317-322. doi: 10.1309/AJCP7KEYGN3OBGQX
[28] Nicholls SJ, Puri R, Anderson T, et al. Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial[J]. JAMA, 2016, 316(22): 2373-2384. doi: 10.1001/jama.2016.16951
[29] Du H, Li X, Su N, et al. Proprotein convertase subtilisin/kexin 9 inhibitors in reducing cardiovascular outcomes: a systematic review and meta-analysis[J]. Heart, 2019, 105(15): 1149-1159.
[30] 帕孜丽亚·阿地力, 穆叶赛·尼加提. 动脉粥样硬化与炎症[J]. 临床心血管病杂志, 2020, 36(4): 303-306. doi: 10.13201/j.issn.1001-1439.2020.04.003
[31] 陆言巧, 沈兰, 何奔. PCSK9抑制剂的机制及其临床进展[J]. 临床心血管病杂志, 2020, 36(1): 14-19. doi: 10.13201/j.issn.1001-1439.2020.01.003
[32] Chinetti-Gbaguidi G, Daoudi M, Rosa M, et al. Human Alternative Macrophages Populate Calcified Areas of Atherosclerotic Lesions and Display Impaired RANKL-Induced Osteoclastic Bone Resorption Activity[J]. Circ Res, 2017, 121(1): 19-30. doi: 10.1161/CIRCRESAHA.116.310262
[33] de Gaetano M, Crean D, Barry M, et al. M1-and M2-Type Macrophage Responses Are Predictive of Adverse Outcomes in Human Atherosclerosis[J]. Front Immunol, 2016, 7: 275.
[34] Barrett TJ. Macrophages in Atherosclerosis Regression[J]. Arterioscler Thromb Vasc Biol, 2020, 40(1): 20-33. doi: 10.1161/ATVBAHA.119.312802
[35] Pagie S, G rard N, Charreau B. Notch signaling triggered via the ligand DLL4 impedes M2 macrophage differentiation and promotes their apoptosis[J]. Cell Commun Signal, 2018, 16(1): 4. doi: 10.1186/s12964-017-0214-x
[36] Yin J, Hu H, Li X, et al. Inhibition of Notch signaling pathway attenuates sympathetic hyperinnervation together with the augmentation of M2 macrophages in rats post-myocardial infarction[J]. Am J Physiol Cell Physiol, 2016, 310(1): C41-C53. doi: 10.1152/ajpcell.00163.2015
[37] 陈羽斐, 沈伟, 施海明. 巨噬细胞免疫代谢与动脉粥样硬化的研究进展[J]. 中国动脉硬化杂志, 2020, 28(1): 74-80. doi: 10.3969/j.issn.1007-3949.2020.01.015
[38] Carneros D, Santamar a EM, Larequi E, et al. Cardiotrophin-1 is an anti-inflammatory cytokine and promotes IL-4-induced M2 macrophage polarization[J]. FASEB J, 2019, 33(6): 7578-7587. doi: 10.1096/fj.201801563R
[39] Marcon R, Bento AF, Dutra RC, et al. Maresin 1, a proresolving lipid mediator derived from omega-3 polyunsaturated fatty acids, exerts protective actions in murine models of colitis[J]. J Immunol, 2013, 191(8): 4288-4298. doi: 10.4049/jimmunol.1202743
[40] Dalli J, Serhan CN. Specific lipid mediator signatures of human phagocytes: microparticles stimulate macrophage efferocytosis and pro-resolving mediators[J]. Blood, 2012, 120(15): e60-e72. doi: 10.1182/blood-2012-04-423525
[41] Gerlach BD, Marinello M, Heinz J, et al. Resolvin D1 promotes the targeting and clearance of necroptotic cells[J]. Cell Death Differ, 2020, 27(2): 525-539. doi: 10.1038/s41418-019-0370-1
[42] Fredman G, Kamaly N, Spolitu S, et al. Targeted nanoparticles containing the proresolving peptide Ac2-26 protect against advanced atherosclerosis in hypercholesterolemic mice[J]. Sci Transl Med, 2015, 7(275): 220r-275r.
[43] Bazan HA, Lu Y, Jun B, et al. Circulating inflammation-resolving lipid mediators RvD1 and DHA are decreased in patients with acutely symptomatic carotid disease[J]. Prostaglandins Leukot Essent Fatty Acids, 2017, 125: 43-47. doi: 10.1016/j.plefa.2017.08.007
[44] Schaller MS, Chen M, Colas RA, et al. Treatment With a Marine Oil Supplement Alters Lipid Mediators and Leukocyte Phenotype in Healthy Patients and Those With Peripheral Artery Disease[J]. J Am Heart Assoc, 2020, 9(15): e16113.
[45] Yurdagul A Jr, Doran AC, Cai B, et al. Mechanisms and Consequences of Defective Efferocytosis in Atherosclerosis[J]. Front Cardiovasc Med, 2017, 4: 86.
[46] Park SJ, Lee KP, Kang S, et al. Sphingosine 1-phosphate induced anti-atherogenic and atheroprotective M2 macrophage polarization through IL-4[J]. Cell Signal, 2014, 26(10): 2249-2258. doi: 10.1016/j.cellsig.2014.07.009
[47] Bi Y, Chen J, Hu F, et al. M2 Macrophages as a Potential Target for Antiatherosclerosis Treatment[J]. Neural Plast, 2019, 2019: 6724903.
[48] Norris PC, Libreros S, Serhan CN. Resolution metabolomes activated by hypoxic environment[J]. Sci Adv, 2019, 5(10): x4895. doi: 10.1126/sciadv.aax4895
[49] Gharib SA, McMahan RS, Eddy WE, et al. Transcriptional and functional diversity of human macrophage repolarization[J]. J Allergy Clin Immunol, 2019, 143(4): 1536-1548. doi: 10.1016/j.jaci.2018.10.046
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