固有免疫应答与动脉粥样硬化关系的研究进展
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摘要
固有免疫应答在动脉粥样硬化(atherosclerosis,As)的发生和发展中起重要作用.固有免疫应答细胞,包括单核/巨噬细胞、肥大细胞、自然杀伤细胞、中性粒细胞和树突状细胞,是机体抵御微生物和异物入侵的第一道防线.这些细胞广泛参与As中泡沫细胞形成、斑块内基质降解、细胞凋亡、血管新生和斑块破裂等事件.模式识别受体是免疫细胞上识别病原体(或某些内源性成分)相关分子模式的一类受体分子,包括Toll样受体和NOD样受体,介导固有免疫应答反应.Toll样受体在固有免疫应答细胞中具有不同程度的表达,在As中具有不同的作用,如TLR2和TLR4对As起促进作用,而TLR3具有As保护作用.NLRP3炎性体与动脉血管壁的早期损伤有关.对固有免疫应答细胞及模式识别受体在As形成中的作用进行深入研究,不仅有助于理解As的形成过程,而且还能为临床上防治心血管类疾病提供了新的治疗靶点和诊断指标.
Innate immune response plays important roles in the lesion initiation and progression of atherosclerosis(As).Innate immune cells,including monocyte/macrophages,mast cells,natural killer cells,neutrophilic granulocytes and dendritic cells,represent the first line of defense against pathogens and foreign agents.These cells have extensive effects involved in foam cell formation,extracellular matrix degradation,cell apoptosis,angiogenesis and As plaque rupture.Pattern recognition receptors,including Toll-like and NOD-like receptors,could mediate innate immune response by recognize pathogen-associated molecular patterns or some endogenous components.TLRs are differentially expressed by the various cell types in atherosclerosis,and have different roles.TLR2 and TLR4 accelerate the progress of atherosclerosis,but the TLR3 induces protection of the atherosclerosis development.NLRP3 inflammasome is related to early arterial wall damages.Further researchs on the roles of the innate immune cells and pattern recognition receptors in atherogenesis help to understanding the formation of atherosclerosis,and also provide novel potential therapeutic and diagnostic targets in the future treatment of cardiovascular disease.
Innate immune response plays important roles in the lesion initiation and progression of atherosclerosis(As).Innate immune cells,including monocyte/macrophages,mast cells,natural killer cells,neutrophilic granulocytes and dendritic cells,represent the first line of defense against pathogens and foreign agents.These cells have extensive effects involved in foam cell formation,extracellular matrix degradation,cell apoptosis,angiogenesis and As plaque rupture.Pattern recognition receptors,including Toll-like and NOD-like receptors,could mediate innate immune response by recognize pathogen-associated molecular patterns or some endogenous components.TLRs are differentially expressed by the various cell types in atherosclerosis,and have different roles.TLR2 and TLR4 accelerate the progress of atherosclerosis,but the TLR3 induces protection of the atherosclerosis development.NLRP3 inflammasome is related to early arterial wall damages.Further researchs on the roles of the innate immune cells and pattern recognition receptors in atherogenesis help to understanding the formation of atherosclerosis,and also provide novel potential therapeutic and diagnostic targets in the future treatment of cardiovascular disease.
引文
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[35]Zernecke A,Bot I,Djalali-Talab Y,et al.Protective role of CXC receptor4/CXC ligand12unveils the importance of neutrophils in atherosclerosis.Circ Res,2008,102(2):209-217
[36]Liu P,Yu Y R,Spencer J A,et al.CX3CR1deficiency impairs dendritic cell accumulation in arterial intima and reduces atherosclerotic burden.Arterioscler Thromb Vasc Biol,2008,28(2):243-250
[37]Shaposhnik Z,Wang X,Weinstein M,et al.Granulocyte macrophage colony-stimulating factor regulates dendritic cell content of atherosclerotic lesions.Arterioscler Thromb Vasc Biol,2007,27(3):621-627
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[39]Smale S T.Transcriptional regulation in the innate immune system.Curr Opin Immunol,2012,24(1):51-57
[40]Olive C.Pattern recognition receptors:sentinels in innate immunity and targets of new vaccine adjuvants.Expert Rev Vaccines,2012,11(2):237-256
[41]Langefeld T,Mohamed W,Ghai R,et al.Toll-like receptors and NOD-like receptors:domain architecture and cellular signalling.Adv Exp Med Biol,2009,653:48-57
[42]Fresno M,Alvarez R,Cuesta N.Toll-like receptors,inflammation,metabolism and obesity.Arch Physiol Biochem,2011,117(3):151-164
[43]Michelsen K S,Wong M H,Shah P K,et al.Lack of Toll-like receptor4or myeloid differentiation factor88reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E.Proc Natl Acad Sci USA,2004,101(29):10679-10684
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[45]Monaco C,Gregan S M,Navin T J,et al.Toll-like receptor-2 mediates inflammation and matrix degradation in human atherosclerosis.Circulation,2009,120(24):2462-2469
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