Weinstein D B, Heider J G
Am J Cardiol. 1987 Jan 30;59(3):163B-172B. doi: 10.1016/0002-9149(87)90097-x.
A generalized accumulation of cholesterol, calcium and matrix materials (collagen, elastin and proteoglycans) occurs in an age-dependent manner in major arteries. Human atherogenesis is a disease of arteries characterized by a focal accumulation of fibrous matrix elements, lipids and calcium at lesion sites. Studies in cholesterol-fed animal models have indicated that calcium competitors and chelating agents can reduce calcium, lipid and matrix accumulation in arterial lesions and reduce the extent of lesion formation. These agents generally alter soft and hard tissue calcium pools or have deleterious side-effect profiles. Antiatherogenic studies with calcium antagonists (which have been shown to be safe in human clinical studies) have created confusion because of conflicting results. It is apparent, however, that high doses of calcium antagonists can significantly decrease atherogenic lesion development in cholesterol-fed rabbits. The antiatherogenic effects of calcium antagonists may be the result of changes in intracellular calcium pools within smooth muscle cells, which may lead to alterations in cellular metabolic activity or may be due to activities not related to calcium channel effects. Several mechanisms involving regulation of lipoprotein receptor synthesis, lipoprotein uptake or degradation, cholesterol ester hydrolytic activity and arterial matrix synthesis are discussed as potential sites of activity for calcium antagonists. A dihydropyridine channel antagonist, PN 200-110 (isradipine), has been shown to be a very potent antiatherogenic agent in the rabbit and also to be a potent inhibitor of smooth muscle cell matrix synthesis.
胆固醇、钙和基质物质（胶原蛋白、弹性蛋白和蛋白聚糖）在主要动脉中以年龄依赖的方式普遍积聚。人类动脉粥样硬化是一种动脉疾病，其特征是病变部位纤维基质成分、脂质和钙的局部积聚。对喂食胆固醇的动物模型的研究表明，钙竞争剂和螯合剂可以减少动脉病变中钙、脂质和基质的积聚，并减少病变形成的程度。这些药物通常会改变软组织和硬组织中的钙库，或者具有有害的副作用。由于结果相互矛盾，使用钙拮抗剂进行的抗动脉粥样硬化研究（已在人体临床研究中证明是安全的）产生了混淆。然而，很明显，高剂量的钙拮抗剂可以显著减少喂食胆固醇的兔子动脉粥样硬化病变的发展。钙拮抗剂的抗动脉粥样硬化作用可能是平滑肌细胞内钙库变化的结果，这可能导致细胞代谢活动的改变，或者可能是由于与钙通道效应无关的活动。讨论了几种涉及脂蛋白受体合成、脂蛋白摄取或降解、胆固醇酯水解活性和动脉基质合成调节的机制，作为钙拮抗剂潜在的作用位点。一种二氢吡啶通道拮抗剂PN 200 - 110（伊拉地平）已被证明在兔子中是一种非常有效的抗动脉粥样硬化药物，也是平滑肌细胞基质合成的有效抑制剂。
