Stoneman Victoria E A, Bennett Martin R
Unit of Cardiovascular Medicine, Addenbrooke's Centre for Clinical Investigation, Level 6, Box 110, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
Clin Sci (Lond). 2004 Oct;107(4):343-54. doi: 10.1042/CS20040086.
Atherosclerotic plaques develop as a consequence of the accumulation of circulating lipid and the subsequent migration of inflammatory cells (macrophages and T-lymphocytes) and VSMCs (vascular smooth muscle cells). Advanced plaques consist of a lipid-rich core, separated from the lumen by a fibrous cap composed of VSMCs, collagen and extracellular matrix. Plaque enlargement ultimately narrows the lumen (stenosis) causing angina. However, recent studies have emphasized that acute coronary syndromes (unstable angina/myocardial infarction) are caused by lesion erosion/rupture with superimposed thrombus formation on often small non-stenotic plaques. Thus current therapies work predominantly on stabilization of plaques rather than plaque regression. Apoptosis (programmed cell death) is increasingly observed as plaques develop, although the exact mechanisms and consequences of apoptosis in the development and progression of atherosclerosis are still controversial. Increased endothelial cell apoptosis may initiate atherosclerosis, whereas apoptosis of VSMCs and macrophages localizes in 'vulnerable' lesions, i.e. those most likely to rupture, and at sites of rupture. This review will focus on the regulation of apoptosis of cells within the vasculature, concentrating on the relevance of apoptosis to plaque progression and clinical consequences of vascular cell apoptosis.
动脉粥样硬化斑块的形成是循环脂质积累以及随后炎症细胞（巨噬细胞和T淋巴细胞）和血管平滑肌细胞（VSMC）迁移的结果。晚期斑块由富含脂质的核心组成，该核心通过由VSMC、胶原蛋白和细胞外基质组成的纤维帽与管腔隔开。斑块增大最终会使管腔变窄（狭窄），导致心绞痛。然而，最近的研究强调，急性冠状动脉综合征（不稳定型心绞痛/心肌梗死）是由病变侵蚀/破裂并在通常较小的非狭窄斑块上叠加血栓形成所致。因此，目前的治疗主要致力于斑块的稳定，而非斑块的消退。随着斑块的发展，越来越多地观察到细胞凋亡（程序性细胞死亡），尽管细胞凋亡在动脉粥样硬化发展和进展中的确切机制及后果仍存在争议。内皮细胞凋亡增加可能引发动脉粥样硬化，而VSMC和巨噬细胞的凋亡则定位于“易损”病变，即那些最有可能破裂的病变以及破裂部位。本综述将聚焦于脉管系统内细胞凋亡的调节，重点关注细胞凋亡与斑块进展的相关性以及血管细胞凋亡的临床后果。
