Apoptosis in atherogenesis: implications for plaque destabilization.

Atherosclerotic plaques in coronary arteries are composed of a crescent-shaped mass of lipids separated from the lumen by a fibrous cap. Loss of smooth muscle cells (SMCs) in the fibrous cap could have serious consequences, since SMCs are the only cells in the cap that can synthesize collagen fibres type I and III. These fibres maintain the tensile strength of the fibrous cap. The role of cell loss and apoptotic cell death in the progression of atherosclerosis has received renewed attention recently in the literature. The large variability in the reported values for the percentage of apoptotic cells in plaques can be explained by the aspecificity of the TUNEL technique used to detect apoptosis. Despite this variability, there is no doubt that both SMCs and macrophages can die in plaques through apoptosis. The significance of macrophage apoptosis is very different from that of SMC apoptosis. Increased apoptosis of SMCs in the vulnerable regions of the plaque can result in weakening of the fibrous cap, whereas increased macrophage apoptosis can lead to plaque stabilization through decreased breakdown of collagen. Cytoplasmic remnants of apoptotic SMCs often remain in the plaque as matrix vesicles. These small calcium-containing vesicles could initiate plaque calcification.