Antiatherogenic properties of calcium antagonists. State of the art.
Atherosclerosis is an arterial disease characterized by localized accumulation of collagen, elastin, lipids, and calcium at sites associated with macrophage infiltration and altered smooth muscle metabolism. Studies in several types of animal models, especially cholesterol-fed rabbits, have shown that calcium competitors, calcium chelators, anticalcifying agents, and calcium antagonists can reduce the accumulation of atherogenic lesion components and decrease the progression of lesions. Although there are some conflicting data in the animal model studies, it is now apparent that several classes of calcium antagonists inhibit the progression of early arterial lesions induced by cholesterol-feeding in animals. The dihydropyridine class of calcium antagonists may be more potent as anti-atherosclerotic agents than the other classes. Mechanisms involving regulation of endothelial cell, smooth muscle cell, and macrophage metabolism may be responsible for the effects of calcium antagonists on early lesion progression. Recent studies in cell culture-model systems suggest that calcium antagonists may significantly alter activities that regulate lipoprotein-derived cholesterol accumulation by arterial wall cells. Some of these activities are independent of calcium flux across voltage-operated calcium channels. Thus, calcium antagonists may reduce the progression of atherogenic lesions by a combination of decreasing calcium accumulation within arterial wall cells and by altering calcium channel-independent metabolic activities, which affect lesion development.
Weinstein
D B
DB
Department of Lipid and Lipoprotein Metabolism, Sandoz Research Institute, East Hanover, New Jersey 07936.
Heider
J G
JG
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control*; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004095:Dihydropyridines / Q000627:therapeutic use; D006801:Humans
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D002784:Cholesterol; D002118:Calcium