Calcium Antagonists and Vascular Smooth Muscle Cells in Atherogenesis

Abstract

Vascular smooth muscle cells (SMCs) play a key role in the development of atherosclerotic lesions. Vascular smooth muscle, however, does not represent a homogeneous tissue. Using myosin as a marker of the differentiation processes in development and in vascular disease, we have been able to demonstrate the existence of distinct SMC populations in rabbit aorta. In our studies, a specific SMC population of the aortic media showing an "immature" type of myosin isoform expression accounted for the majority of SMCs present in the atherosclerotic plaque. Nifedipine, a dihydropyridine-derived calcium antagonist, was able to decrease the size of this particular SMC population and to prevent the development of atherosclerotic lesions in hypercholesterolemic rabbits. Here we report about a similar effect obtained by treating hypercholesterolemic rabbits with nitrendipine, another dihydropyridine-derived calcium antagonist. This article also summarizes the main experimental and clinical studies conducted on the antiatherogenic effect of calcium antagonists and focuses on the mechanisms underlying this effect, particularly at the vascular SMC level.