769-6 Inhibitory Effect of Lovastatin on Human Coronary Smooth Muscle Cell Proliferation

Abstract

Longterm administration of lipid lowering agents has been shown to cause regression of coronary atherosclerosis. To evaluate the mechanism of such regression, we studied the effect of Lovastatin (HMG coenzyme A reductase inhibitor) on the smooth muscle cells cultured from atherosclerotic plaque obtained from 5 human coronary arteries undergoing directional coronary atherectomy for de novo lesions. Arterial smooth muscle cell lines were created by 3–5 passages. These cells were then placed at a density of 3000 cells/ml in M-199 medium with 10% fetal bovine serum. They were exposed to Lovastatin at varying concentrations between 10 -9 to 10 -4 M. The coronary arterial smooth muscle cells were inhibited in a dose dependent manner. The table below shows the actual cell counts at various concentrations of Lovastatin in the 5 patients. Effect of Lovastatin on smooth muscle cell proliferation PT Control Mitogen 10 -9 10 -8 10 -7 10 -6 10 -5 10 -4 M J.B. 2575 5216 4325 3875 3320 2975 2575 1901 M.P 2879 4390 4125 3979 3629 3098 2095 1971 I.H. 2389 3613 3368 3153 2841 2221 2006 1696 M.L. 2900 5938 4817 3909 3199 2729 2072 1092 W.C. 2830 3729 3210 2710 2093 1773 1292 934 Mean 2715 4581 3969 3525 3016 2559 2008 1519 HMG Coenzyme A reductase inhibitor Lovastatin has a strong antiporliferative effect on human coronary smooth muscle cells. These observations suggest that antiproliferative effect of Lovastatin may be responsible for causing regression of atherosclerotic lesions in addition to its lipid lowering effects.