The role of apoptosis in vascular disease

Normal arteries are characterized by a low turnover of endothelial (EC) and smooth muscle cells (SMC). Different mechanisms protect the EC and SMC aga inst apoptosis in the normal artery. In hypertension, SMC replication is in creased but this is not counterbalanced by increased apoptosis, resulting i n thickening of the media of arteries and arterioles, The significance of a poptosis in atherosclerosis depends on the stage of the plaque, localizatio n and the cell types involved. Both macrophages and SMC undergo apoptosis i n atherosclerotic plaques. Apoptosis of macrophages is mainly present in re gions showing signs of DNA synthesis/repair, SMC apoptosis is mainly presen t in less cellular regions and is not associated with DNA synthesis/repair, Even in the early stages of atherosclerosis SMC become susceptible to apop tosis since they increase different pro-apoptotic factors. Moreover, recent data indicate that SMC may be killed by activated macrophages. The loss of the SMC can be detrimental for plaque stability since most of the intersti tial collagen fibres, which are important for the tensile strength of the f ibrous cap, are produced by SMC. Apoptosis of macrophages could be benefici al for plaque stability if apoptotic bodies were removed. Apoptotic cells t hat are not scavenged in the plaque activate thrombin, which could further induce intraplaque thrombosis. It can be concluded that apoptosis in primar y atherosclerosis is detrimental since it could lead to plaque rupture and thrombosis. Recent data of our group indicate that apoptosis decreased afte r Lipid lowering,which could be important in the understanding of the cell biology of plaque stabilization. Copyright (C) 2000 John Wiley & Sons, Ltd.