Abstract
Apoptosis is a genetically controlled, cell autonomous pathway for cellular demise with distinct ligands, signaling pathways and characteristic morphologic alterations. It may determine the evolution, progression and biologic behavior of atherosclerotic lesions. Prior to the appearance of atherosclerotic lesions, endothelial cell apoptosis may be the basis of endothelial dysfunction that often precedes the formation of macroscopic lesions. In early lesions, it is plausible that a biphasic pattern of cellular turnover involving apoptosis may modulate cellular growth and senescence in early years of postnatal life. The progression of fatty streaks may depend on cellular content and extent of oxidization of LDL that may influence the rate of foam cell apoptosis and removal of cellular debris. In established atherosclerotic lesions apoptosis of different cell types may contribute to plaque erosion (endothelial cells), plaque progression (macrophages and T cells) and plaque thinning and rupture (VSMCs and macrophages). The exact role of apoptosis in acute ischemic events, however, remains unresolved. Visualization of apoptotic macrophages at sites of plaque rupture suggests a role in precipitating acute events. On the other hand, it appears that some strategies that limit atherosclerosis tend to increase macrophage and VSMC apoptosis. Macrophage apoptosis, by removing a potent source of inflammatory cytokines from the lesion, can favorably influence disease progression. Modulation of apoptosis as a therapeutic tool in atherosclerosis requires further studies to elucidate the molecular pathways and cellular signaling involved in apoptotic cell death.
Keywords: restenosis, smooth muscle cells(smcs), atherogenic, atherosclerotic disease, tumor necrosis factor (tnf), anti-apoptotic proteins, adapter molecules, caspase-independent pathways, macrophages, oxidized-ldl
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