[HTML][HTML] 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors attenuate vascular smooth muscle proliferation by preventing rho GTPase-induced down-regulation of …

U Laufs, D Marra, K Node, JK Liao - Journal of Biological Chemistry, 1999 - ASBMB
The mechanism by which platelet-derived growth factor (PDGF) regulates vascular smooth
muscle cell (SMC) DNA synthesis is unknown, but may involve isoprenoid intermediates of
the cholesterol biosynthetic pathway. Inhibition of isoprenoid synthesis with the 3-hydroxy-3-
methylglutaryl-CoA reductase inhibitor, simvastatin (Sim, 1–10 μm), inhibited PDGF-induced
SMC DNA synthesis by> 95%, retinoblastoma gene product hyperphosphorylation by 90%,
and cyclin-dependent kinases (cdk)-2,-4, and-6 activity by 80±5, 50±3, and 48±3 …