Role of apoptosis in atherosclerosis and its therapeutic implications.
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.
Stoneman
Victoria E A
VE
Unit of Cardiovascular Medicine, Addenbrooke's Centre for Clinical Investigation, Level 6, Box 110, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. veas2@mole.bio.cam.ac.uk
Bennett
Martin R
MR
D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001161:Arteriosclerosis / Q000188:drug therapy / Q000473:pathology*; D042783:Endothelial Cells / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008264:Macrophages / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000473:pathology
D000975:Antioxidants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors