Effects of Calcium Antagonists on Atherogenesis

Calcium antagonists are able to reduce the development of atherosclerotic lesions in many animal models of atherosclerosis. Although the precise mechanisms of their antiatherogenic effects are unknown studies have shown interference with several pathogenetic mechanisms of the atherosclerotic disease process, namely preservation of endothelial integrity, reduced smooth muscle cell migration and proliferation, increased low density lipoprotein uptake and degradation in smooth muscle cells and reduced synthesis of matrix components. Many of these effects are unrelated to their blocking effects on voltage-dependent slow calcium channels, and most effects have been observed with very high concentrations only. Furthermore, differing calcium antagonists seem to influence these mechanisms differently but available data are difficult to interpret because of differences in study design and models used. With the exception of data on calcium antagonists for secondary prevention after myocardial infarction and their influence on the rate of restenosis after percutaneous transluminal angioplasty, no data are available in man with respect to a possible influence on atherosclerosis. Results from on-going studies designed to address specifically this issue must be awaited to answer the question whether the experimental findings can be extended to human atherosclerosis.