Tedgui Alain, Mallat Ziad
Institut National de la Santé et de la Recherche Médicale U. 689, Cardiovascular Research Center Lariboisiere, and University Paris 7, Paris, France.
Physiol Rev. 2006 Apr;86(2):515-81. doi: 10.1152/physrev.00024.2005.
Atherosclerosis is a chronic disease of the arterial wall where both innate and adaptive immunoinflammatory mechanisms are involved. Inflammation is central at all stages of atherosclerosis. It is implicated in the formation of early fatty streaks, when the endothelium is activated and expresses chemokines and adhesion molecules leading to monocyte/lymphocyte recruitment and infiltration into the subendothelium. It also acts at the onset of adverse clinical vascular events, when activated cells within the plaque secrete matrix proteases that degrade extracellular matrix proteins and weaken the fibrous cap, leading to rupture and thrombus formation. Cells involved in the atherosclerotic process secrete and are activated by soluble factors, known as cytokines. Important recent advances in the comprehension of the mechanisms of atherosclerosis provided evidence that the immunoinflammatory response in atherosclerosis is modulated by regulatory pathways, in which the two anti-inflammatory cytokines interleukin-10 and transforming growth factor-beta play a critical role. The purpose of this review is to bring together the current information concerning the role of cytokines in the development, progression, and complications of atherosclerosis. Specific emphasis is placed on the contribution of pro- and anti-inflammatory cytokines to pathogenic (innate and adaptive) and regulatory immunity in the context of atherosclerosis. Based on our current knowledge of the role of cytokines in atherosclerosis, we propose some novel therapeutic strategies to combat this disease. In addition, we discuss the potential of circulating cytokine levels as biomarkers of coronary artery disease.
动脉粥样硬化是一种涉及固有免疫和适应性免疫炎症机制的动脉壁慢性疾病。炎症在动脉粥样硬化的各个阶段都至关重要。它与早期脂肪条纹的形成有关，此时内皮细胞被激活并表达趋化因子和黏附分子，导致单核细胞/淋巴细胞募集并浸润到内皮下。炎症在不良临床血管事件发作时也起作用，此时斑块内的活化细胞分泌基质蛋白酶，降解细胞外基质蛋白并削弱纤维帽，导致破裂和血栓形成。参与动脉粥样硬化过程的细胞分泌并被称为细胞因子的可溶性因子激活。对动脉粥样硬化机制理解的重要最新进展表明，动脉粥样硬化中的免疫炎症反应受调节途径调控，其中两种抗炎细胞因子白细胞介素-10和转化生长因子-β起关键作用。本综述的目的是汇集有关细胞因子在动脉粥样硬化发生、发展和并发症中作用的当前信息。特别强调促炎和抗炎细胞因子在动脉粥样硬化背景下对致病性（固有和适应性）免疫及调节性免疫的贡献。基于我们目前对细胞因子在动脉粥样硬化中作用的认识，我们提出了一些对抗这种疾病的新治疗策略。此外，我们讨论了循环细胞因子水平作为冠状动脉疾病生物标志物的潜力。
