PHARMACOLOGICAL TREATMENT OF ATHEROSCLEROSIS - BEYOND LIPID-LOWERING THERAPY

Increased proliferation of intimal smooth muscle cells (SMCs), resulti ng in myointimal hyperplasia and luminal narrowing, is a characteristi c of the early phase of atherogenesis. Since agents that reduce this p rocess could potentially be considered as alternatives to lipid-loweri ng therapy in the prevention/treatment of atherosclerosis, it is of in terest to elucidate the mechanisms involved in myointimal proliferatio n. This review focuses on the main mechanisms that control vascular SM C reactivity/proliferation with particular reference to spontaneously hypertensive rat-derived arterial cells, which exhibit exaggerated gro wth and hyperresponsiveness to stimuli compared with cells from normot ensive Wistar-Kyoto rats. In view of the fact that overall cell reacti vity is under the control of free Ca2+ ions, the beneficial effects of calcium antagonists on the prevention/treatment of atherosclerosis ar e discussed. In particular, the mechanisms whereby amlodipine-a vascul ar selective inhibitor of inward Ca2+ current carried by the L-type Ca 2+ channels-can affect cell growth and exhibit antiatherogenic propert ies are reviewed. (C) 1997 Elsevier Science Ireland Ltd.