赵晨,贾海波,李丽丽

• 1:哈尔滨医科大学附属第二医院心血管内科

摘要(Abstract)：

<正>冠状动脉粥样硬化通常被认为是一种慢性炎症性疾病,可导致不同程度的血流通过障碍。病变部位有特异性形成的纤维帽覆盖于富含脂质成分的斑块核心区域。病变早期通常有完整的内皮覆盖,而在病变晚期,内皮连续性遭到破坏,这导致了病变进展及严重并发症的形成。通过对动脉粥样硬化机制进行研究发现,包括巨噬细胞和T细胞等多种细胞可表现出持续的炎症反应性,产生多种炎性介质,如:促炎细胞因子、免疫激活的共刺激因子等[1-2]。此外,许多巨噬细胞可通过清道夫受体内化胆固醇,甚至部分可产生抗炎因子,而部分T细胞也可表现出抗炎和免疫抑制的特性。这些促炎和抗炎机制共同导致了冠状动脉粥样硬化病变进展缓慢、难以治愈以及

关键词(KeyWords)： 易损斑块;炎症;斑块破裂;斑块侵蚀

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金青年科学基金(81700234);国家自然科学基金面上项目(81671763)

作者(Author): 赵晨,贾海波,李丽丽

参考文献(References)：

• [1] Hansson GK, Hermansson A. The immune system in atherosclerosis.Nat Immunol, 2011, 12(3):204-212.
• [2] Libby P, Lichtman AH, Hansson GK. Immune eff ector mechanisms implicated in atherosclerosis:from mice to humans. Immunity,2013, 38(6):1092-1104.
• [3] Libby P, Tabas I, Fredman G, et al. Inflammation and its resolution as determinants of acute coronary syndromes. Circ Res, 2014, 114(12):1867-1879.
• [4] Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature, 2011, 473(7347):317-325.
• [5] Kieboom BC, Niemeijer MN, Leening MJ, et al. Serum magnesium and the risk of death from coronary heart disease and sudden cardiac death. J Am Heart Assoc, 2016, 5(1). pii:e002707.
• [6] Virmani R, Kolodgie FD, Burke AP, et al. Lessons from sudden coronary death:a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol,2000, 20(5):1262-1275.
• [7] Vakili H, Shirazi M, Charkhkar M, et al. Correlation of plateletto-lymphocyte ratio and neutrophil-to-lymphocyte ratio with thrombolysis in myocardial inf arction f rame count in STsegment elevation myocardial infarction. Eur J Clin Invest,2017, 47(4):322-327.
• [8] Durham AL, Speer MY, Scatena M, et al. Role of smooth muscle cells in vascular calcification:implications in atherosclerosis and arterial stiff ness. Cardiovasc Res, 2018, 114(4):590-600.
• [9] Preisser L, Miot C, Le Guillou-Guillemette H, et al. IL-34 and macrophage colony-stimulating factor are overexpressed in hepatitis C virus fibrosis and induce profibrotic macrophages that promote collagen synthesis by hepatic stellate cells. Hepatology, 2014, 60(6):1879-1890.
• [10] Sakamoto K, Kim MJ, Rhoades ER, et al. Mycobacterial trehalose dimycolate reprograms macrophage global gene expression and activates matrix metalloproteinases. Infect Immun, 2013, 81(3):764-776.
• [11] Choi YH, Hong YJ, Ahn Y, et al. Relationship between neutrophil-to-lymphocyte ratio and plaque components in patients with coronary artery disease:virtual histology intravascular ultrasound analysis. J Korean Med Sci, 2014, 29(7):950-956.
• [12]周蓉，樊蓉，沈霞蔚.中性粒细胞与淋巴细胞比值与冠状动脉临界病变患者斑块易损性的相关性研究.中国循证心血管医学杂志，2019, 11(2):230-233.
• [13]涂应锋，唐昊，于波.基于光学相干断层成像的多模、多功能成像在评估易损斑块中的作用.中国介入心脏病学杂志，2019, 27(3):174-177.
• [14]颜红兵，霍勇.冠状动脉影像学和生理学的现状与未来.中国介入心脏病学杂志，2019, 27(5):241-242.
• [15] Tian J, Dauerman H, Toma C, et al. Prevalence and characteristics of TCFA and degree of coronary artery stenosis:an OCT, IVUS,and angiographic study. J Am Coll Cardiol, 2014, 64(7):672-680.
• [16] Falk E, Nakano M, Bentzon JF, et al. Update on acute coronary syndromes:the pathologists’view. Eur Heart J, 2013, 34(10):719-728.
• [17] Kubo T, Tanaka A, Ino Y, et al. Assessment of coronary atherosclerosis using optical coherence tomography. J Atheroscler Thromb, 2014, 21(9):895-903.
• [18] Karadimou G, Folkersen L, Berg M, et al. Low TLR7 gene expression in atherosclerotic plaques is associated with major adverse cardio-and cerebrovascular events. Cardiovasc Res, 2017,113(1):30-39.
• [19] Quillard T, Araujo HA, Franck G, et al. TLR2 and neutrophils potentiate endothelial stress, apoptosis and detachment:implications for superficial erosion. Eur Heart J, 2015, 36(22):1394-1404.
• [20] Jia H, Dai J, Hou J, et al. Eff ective anti-thrombotic therapy without stenting:intravascular optical coherence tomography-based management in plaque erosion(the EROSION study). Eur Heart J,2017, 38(11):792-800.
• [21] Xing L, Yamamoto E, Sugiyama T, et al. EROSION study(ef fective anti-thrombotic therapy without stenting:intravascular optical coherence tomography-based management in plaque erosion):a1-year follow-up report. Circ Cardiovasc Interv, 2017, 10(12).pii:e005860.
• [22] Bentzon JF, Otsuka F, Virmani R, et al. Mechanisms of plaque formation and rupture. Circ Res, 2014, 114(12):1852-1866.
• [23] Ceneri N,Zhao L, Young BD, et al. Rac2 modulates atherosclerotic calcification by regulating macrophage interleukin-1beta production.Arterioscler Thromb Vasc Biol, 2017, 37(2):328-340.
• [24] Hu XP, Xie Q, Chen CF, et al. Let-7a Inhibits T-Cell Proliferation a n d I F N-ga m m a sec r e t io n b y d o w n-r eg u la t i n g STAT3expression in patients with psoriasis. Cell Physiol Biochem,2017, 42(1):115-125.
• [25] Klingenberg R, Gerdes N, Badeau RM, et al. Depletion of FOXP3+regulatory T cells promotes hypercholesterolemia and atherosclerosis. J Clin Invest, 2013, 123(3):1323-1334.
• [26] Macleod AS, Hemmers S, Garijo O, et al. Dendritic epidermal T cells regulate skin antimicrobial barrier function. J Clin Invest,2013, 123(10):4364-4374.
• [27] Gistera A, Robertson AK, Andersson J, et al. Transforming growth factor-beta signaling in T cells promotes stabilization of atherosclerotic plaques through an interleukin-17-dependent pathway. Sci Transl Med,2013, 5(196):196ra00.
• [28] Viana GM, Buri MV, Paredes-Gamero EJ, et al. Impaired hematopoiesis and disrupted monocyte/macrophage homeostasis in mucopolysaccharidosis type i mice. J Cell Physiol, 2016, 231(3):698-707.
• [29] Wolf D, Hohmann JD, Wiedemann A, et al. Binding of CD40L to Mac-1's I-domain involves the EQLKKSKTL motif and mediates leukocyte recruitment and atherosclerosis--but does not affect immunity and thrombosis in mice. Circ Res, 2011, 109(11):1269-1279.
• [30] Samuelsson B. Role of basic science in the development of new medicines:examples from the eicosanoidfield. J Biol Chem, 2012,287(13):10070-10080.
• [31] Mackenzie KF, Clark K, Naqvi S, et al. PGE(2)induces macrophage IL-10 production and a regulatory-like phenotype via a protein kinase A-SIK-CRTC3 pathway. J Immunol, 2013, 190(2):565-577.
• [32] Fan Y, Chen Y, Zhang J, et al. Protective role of RNA helicase DEAD-box protein 5 in smooth muscle cell proliferation and vascular remodeling. Circ Res, 2019, 124(10):e84-e100.
• [33] Lemurell M, Ulander J, Emtenas H, et al. Novel chemical series of5-lipoxygenase-activating protein inhibitors for treatment of coronary artery disease. J Med Chem, 2019, 62(9):4325-4349.
• [34] Ingelsson E, Yin L, Back M. Nationwide cohort study of the leukotriene receptor antagonist montelukast and incident or recurrent cardiovascular disease. J Allergy Clin Immunol, 2012, 129(3):702-707. e2.
• [35] Petri MH, Laguna-Fernandez A, Gonzalez-Diez M, et al. The role of the FPR2/ALX receptor in atherosclerosis development and plaque stability. Cardiovasc Res, 2015, 105(1):65-74.
• [36] Ling MY, Ma ZY, Wang YY, et al. Up-regulated ATP-sensitive potassium channels play a role in increased inflammation and plaque vulnerability in macrophages. Atherosclerosis, 2013, 226(2):348-355.
• [37] Chong PP, Selvaratnam L, Abbas AA, et al. Human peripheral blood derived mesenchymal stem cells demonstrate similar characteristics and chondrogenic differentiation potential to bone marrow derived mesenchymal stem cells. J Orthop Res, 2012, 30(4):634-642.
• [38] Mantovani A, Garlanda C, Locati M. Macrophage diversity and polarization in atherosclerosis:a question of balance. Arterioscler Thromb Vasc Biol, 2009, 29(10):1419-1423.
• [39] Imanishi T, Akasaka T. Novel strategies to target inflammatory processes in atherosclerosis. Curr Pharm Des, 2013, 19(9):1616-1625.
• [40] Liao X, Sluimer JC, Wang Y, et al. Macrophage autophagy plays a protective role in advanced atherosclerosis. Cell Metab, 2012, 15(4):545-553.
• [41] Di M, Wang L, Li M, et al. Dickkopf1 destabilizes atherosclerotic plaques and promotes plaque formation by inducing apoptosis of endothelial cells through activation of ER stress. Cell Death Dis,2017, 8(7):e2917.
• [42] Wang Y, Subramanian M, Yurdagul A, et al. Mitochondrialfission promotes the continued clearance of apoptotic cells by macrophages.Cell, 2017, 171(2):331-345. e22.