Pharmacologic treatment of atherosclerosis: beyond lipid-lowering therapy

Increased proliferation of intimal smooth muscle cells (SMCs), resulting in myointimal hyperplasia and luminal narrowing, is a characteristic of the early phase of atherogenesis. Since agents that reduce this process could potentially be considered as alternatives to lipid-lowering therapy in the prevention/treatment of atherosclerosis, it is of interest to elucidate the mechanisms involved in myointimal proliferation. This review focuses on the main mechanisms that control vascular SMC reactivity/proliferation with particular reference to spontaneously hypertensive rat-derived arterial cells, which exhibit exaggerated growth and hyperresponsiveness to stimuli compared with cells from normotensive Wistar–Kyoto rats. In view of the fact that overall cell reactivity is under the control of free Ca2+ ions, the beneficial effects of calcium antagonists on the prevention/treatment of atherosclerosis are discussed. In particular, the mechanisms whereby amlodipine—a vascular selective inhibitor of inward Ca2+ current carried by the L-type Ca2+ channels—can affect cell growth and exhibit antiatherogenic properties are reviewed.