Inhibition of Smooth Muscle Cell Migration and Proliferation by Statins
Vascular smooth muscle cell (SMC) migration and proliferation contribute to the pathobiology of atherosclerosis and of instent restenosis, transplant vasculopathy and vein by-pass graft failure. Since mevalonate (MVA) and other intermediates of cholesterol biosynthesis (isoprenoids) are necessary for cell migration and proliferation, inhibition of 3-methyl-3-glutaryl-coenzyme A (HMG-CoA) reductase, the rate limiting step of the MVA pathway, has the potential to result in antiatherosclerotic effects. Indeed statins, competitive inhibitors of the HMG-CoA reductase, have shown the capability to interfere with migration and proliferation of SMC in diverse experimental models. Here we summarize in vitro, in vivo, and ex vivo evidence of the inhibitory effects of statins on SMC proliferation and migration and discuss the molecular mechanisms involved in their pharmacodynamic action. Altogether, this evidence suggests direct vascular antiatherosclerotic properties of statins. However, it is important to mention that statins failed to prevent intimal thickening when studied in clinical setting characterized by accelerated vascular SMC proliferation and migration (e.g. restenosis after PTCA and instent restenosis), thus leaving open the question of the clinical relevance of these direct vascular effects of statins.
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Document Type: Research Article
Publication date: 2008-06-01
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