Fleckenstein-Grün G, Thimm F, Frey M, Czirfusz A
Physiology Institute, University of Freiburg, FRG.
Basic Res Cardiol. 1994;89 Suppl 1:145-59. doi: 10.1007/978-3-642-85660-0_14.
Chemical microanalyses of conventional human coronary artery plaques (stages I-III [WHO]) revealed the correlation between progressive mural Ca overload up to excessive degrees, and the severity of plaque formation, whereas only small amounts of cholesterol were found, even in complicated lesions. The pathogenetic role of Ca was tested in three types of experimental arteriosclerosis and atheromatosis, using Ca antagonists (verapamil, nitrendipine, diltiazem) as research tools: 1) The Ca type, in vitamin D3 plus nicotine-treated rats; 2) the cholesterol type, in cholesterol-fed New Zealand rabbits; 3) mixed types, in SHRs and NaCl-fed Dahl-S rats. Types (1) and (3) were demonstrated to be governed by a progressive arterial Ca uptake that could be established already in early lesions. The increased mural Ca supply promoted cellular necroses, migration, and proliferation, as well as calcification and degradation of elastic fibers. Ca antagonists prevented the increased Ca incorporation into arterial walls and inhibited the development of experimental arterioscleroses of types (1) and (3). Ca antagonists did not protect coronary arteries of cholesterol-fed rabbits (type [2]) from occlusive cholesterol accumulation. The data suggest an important pathogenetic role of Ca and pronounced antiarteriosclerotic potencies of Ca antagonists in Ca-dominated types of experimental arteriosclerosis. The significance of the present results for pathophysiology and therapy of conventional human arteriosclerosis remains to be clarified.
对传统人类冠状动脉斑块（世界卫生组织I - III期）进行的化学微量分析显示，直至过度程度的进行性血管壁钙超载与斑块形成的严重程度之间存在相关性，而即使在复杂病变中也仅发现少量胆固醇。使用钙拮抗剂（维拉帕米、尼群地平、地尔硫䓬）作为研究工具，在三种类型的实验性动脉硬化和动脉粥样硬化中测试了钙的致病作用：1）维生素D3加尼古丁处理的大鼠中的钙型；2）喂食胆固醇的新西兰兔中的胆固醇型；3）自发性高血压大鼠（SHRs）和喂食氯化钠的达尔盐敏感性大鼠（Dahl - S rats）中的混合型。已证明类型（1）和（3）受早期病变中即可出现的进行性动脉钙摄取支配。血管壁钙供应增加促进了细胞坏死、迁移和增殖，以及弹性纤维的钙化和降解。钙拮抗剂可防止钙更多地掺入动脉壁，并抑制类型（1）和（3）的实验性动脉硬化的发展。钙拮抗剂不能保护喂食胆固醇的兔子的冠状动脉（类型[2]）免受闭塞性胆固醇积累的影响。数据表明钙在以钙为主导的实验性动脉硬化类型中具有重要的致病作用，且钙拮抗剂具有显著的抗动脉硬化效力。目前结果对传统人类动脉硬化的病理生理学和治疗的意义仍有待阐明。
