Yonsei Med J.  1995 Jun;36(3):251-261. 10.3349/ymj.1995.36.3.251.

The effect of lovastatin on proliferation of cultured rat mesangial and aortic smooth muscle cells

• Choi KH
• Kang SW
• Lee SW
• Lee HY
• Han DS
• Kang BS

• KMID: 1123180
• DOI: http://doi.org/10.3349/ymj.1995.36.3.251

Abstract

In order to investigate the anti-proliferative effect of 3-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.

Keyword

Lovastain; rat mesangial cell; aortic smooth muscle cell; proliferation

MeSH Terms

Angiotensin II/pharmacology
Animal
Aorta/cytology/drug effects
Cell Division/drug effects
Cells, Cultured
Endothelins/pharmacology
Glomerular Mesangium/cytology/*drug effects
Lovastatin/*pharmacology
Male
Muscle, Smooth, Vascular/cytology/*drug effects
Platelet-Derived Growth Factor/pharmacology
Rats
Rats, Sprague-Dawley
Support, Non-U.S. Gov't
Thymidine/metabolism