Antiproliferative Effect of Lovastatin on Vascular Smooth Muscle Cell

Park, Seung Woo; Kim, Duk Kyung; Huh, Jeong Eun; Choi, Yoon Hyuk; Choi, Yoon Ho; Gwon, Hyeon Cheol; Kim, June Soo; Lee, Sang Hoon; Hong, Kyung Pyo; Park, Jeong Euy; Seo, Jung Don; Lee, Won Ro

Abstract

BACKGROUND AND OBJECTIVES
This study was performed to investigate the antiproliferative effect of lovastatin on vascular smooth muscle cell, especially to determine whether lovastatin induces apoptosis in vascular smooth muscle cell and the products of mevalonate pathway can reverse the antiproliferative effect of lovastatin.
METHODS
AND MATERIALS: Lovastatin only and lovastatin with one of the products of mevalonate pathway such as isopentenyl adenine, farnesol, mevalonate, cholesterol were added respectively in cultured rat vascular smooth muscle cells stimulated with 10% fetal calf serum. DNA synthesis was measured by tritiated-thymidine incorporation. Cell number was determined by hemocytometric counting. Cells were Giemsa-stained to evaluate morphological changes of apoptosis. Extracted DNA from the cells treated with lovastatin was assessed by gel electrophoresis.
RESULTS
1)Lovastatin inhibited DNA synthesis and cell proliferation in a dose-dependent manner. 2)The inhibitory effects of lovastatin could be reversed almost completely by mevalonate, partially by farnesol. 3)Lovastatin-treated vascular smooth muscle cells showed typical morphological changes of apoptosis. 4)A distinct ladder of DNA bands was visualized by gel electrophoresis of the DNA from the cells treated with lovastatin.
CONCLUSION
Mevalonate metabolism is essential for vascular smooth muscle cell proliferation. The antiproliferative effect of lovastatin may result from the induction of apoptosis in vascular smooth muscle cells.