[Programmed cellular death and atherogenesis: from molecular mechanisms to clinical aspects].
Numerous recent investigations on the development and morphology of atherosclerotic lesions have shown programmed cell death or apoptosis to be an important factor in atherogenesis. Enzymes known as caspases are essential for completion of the apoptotic program. With regard to the origin of signals inducing apoptosis, there are two ways of initiating caspase activation: (a) cellular death receptor-mediated activation; and (b) activation mediated by mitochondrial permeability and expression of the p53 oncogene. Both of these pathways are involved in atherogenesis. Oxidative stress, angiotensin II and cholesterol overload are the primary factors that induce apoptosis in vascular cells. Considering apoptosis in endothelial cells, exposed phosphatidylserine on the cell membrane activates thrombin increasing the probability of arterial thromboses. Further progression of atherosclerosis is promoted by the formation of apoptotic bodies with oxidized phospholipids exposed on the membrane; these also activate adhesion of monocytes. Apoptosis of smooth muscle cells is usually observed in the fibrous portion of an atherosclerotic plaque in which the cells produce collagen important for plaque stability. As apoptosis occurs in smooth muscle cells, the fibrous cap grows thinner. This can result in both plaque rupture, formation of thrombi as well as calcification of the plaque from apoptotic smooth muscle cells remnants. Smooth muscle cells apoptosis is beneficial in that it offers protection to the walls of arteries against proliferative restenosis induced by invasive procedures. Apoptosis of macrophages contributes to the formation and progression of the lipidic core and promotes thrombosis of atherosclerosis in damaged arteries. By contrast, apoptosis of macrophages diminishes the production of matrix methaloproteinases that decompose collagen fibers. New facts concerning the effects of antioxidants (selenium, vitamin C and vitamin E), inhibitors of angiotensin converting enzyme, beta-blockers, calcium chanel blockers, and statins are also considered in this review.
Lesauskaite
Vaiva
V
Institute of Cardiology, Kaunas University of Medicine, Sukileliu 17, 3007 Kaunas, Lithuania. vaivales@kmu.lt
Ivanoviene
Laima
L
Valanciūte
Angelija
A
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000804:Angiotensin II / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D020169:Caspases / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008264:Macrophages / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D002121:Calcium Channel Blockers; D000960:Hypolipidemic Agents; D000804:Angiotensin II; D002784:Cholesterol; D020169:Caspases