Weinstein D B, Heider J G
Department of Lipid and Lipoprotein Metabolism, Sandoz Research Institute, East Hanover, New Jersey 07936.
Am J Med. 1989 Apr 17;86(4A):27-32. doi: 10.1016/0002-9343(89)90186-1.
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.
动脉粥样硬化是一种动脉疾病，其特征在于在与巨噬细胞浸润和改变的平滑肌代谢相关的部位局部积累胶原蛋白、弹性蛋白、脂质和钙。在几种类型的动物模型中进行的研究，特别是喂食胆固醇的兔子，表明钙竞争者、钙螯合剂、抗钙化剂和钙拮抗剂可以减少动脉粥样硬化病变成分的积累并减缓病变的进展。尽管在动物模型研究中有一些相互矛盾的数据，但现在很明显，几类钙拮抗剂可以抑制动物喂食胆固醇诱导的早期动脉病变的进展。二氢吡啶类钙拮抗剂作为抗动脉粥样硬化药物可能比其他类更有效。涉及调节内皮细胞、平滑肌细胞和巨噬细胞代谢的机制可能是钙拮抗剂对早期病变进展产生影响的原因。最近在细胞培养模型系统中的研究表明，钙拮抗剂可能会显著改变调节动脉壁细胞脂蛋白衍生胆固醇积累的活性。其中一些活性与跨电压门控钙通道的钙通量无关。因此，钙拮抗剂可能通过减少动脉壁细胞内的钙积累以及改变影响病变发展的与钙通道无关的代谢活性的组合来减缓动脉粥样硬化病变的进展。
