Department of Internal Medicine , College of Medicine , Yonsei University , Seoul , Korea .
Yonsei Med J 36 : 251-61 ( 1995)
Abstract
In order to investigate the anti-proliferative effect of -hydroxy-3-methylglutaryl coenzyme .
A reductase inhibitor , we evaluated the effects of lovastatin on DNA replication and the proliferation of rat mesangial and aortic smooth muscle cells , both of which were mesenchymal origin cells .
Proliferations were determined by measuring [ 3H]thymidine uptake , and counting the number of cells .
Growth-arrested mesangial and aortic smooth muscle cells were exposed to platelet-derived growth factor ( PDGF ) , endothelin ( ET ) and angiotensin II ( Ang II ) to stimulate mitogenesis .
All agents exhibited dose-dependent stimulation of [ 3H ] thymidine uptake .
PDGF was more potent than the others .
Ang II increased [ 3H ] thymidine uptake without demonstrable mitogenic activity .
Lovastatin inhibited PDGF ( 10 ng/ml in mesangial cell , 25 ng/ml in smooth muscle cell)- , ET ( 10(-7)M)- and Ang II ( 10(-7)M)-induced [ 3H ] thymidine uptake significantly in a dose-dependent manner in both cells .
The increase of cell number in response to PDGF and ET treatment were also inhibited at 10 microM of lovastatin .
The inhibitory effect of lovastatin was largely overcome in the presence of exogenous mevalonate at 200 microM , with 75.5% restoration from lovastatin-induced inhibition on PDGF-induced [ 3H ] thymidine uptake in mesangial cells ( 77.8% in aortic smooth muscle cells ) .
However , the addition of cholesterol did not prevent inhibition by lovastatin .
In conclusion , lovastatin had an inhibitory effect on mesangial and aortic smooth muscle cell proliferation , and mevalonate was essential for DNA replication in both types of cells .
Lovastatin may reduce glomerular and atherosclerotic injury through an anti-proliferative effect on mesangial and vascular smooth muscle cells , in addition to lowering circulating lipids .