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.
Marche
P
P
CNRS, Université René Descartes, Paris, France. marche@necker.fr
Hérembert
T
T
Zhu
D L
DL
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D002121:Calcium Channel Blockers; D000960:Hypolipidemic Agents; D008055:Lipids; D002118:Calcium