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The migration and proliferation of vascular smooth muscle cells (SMCs) are known to play roles in the pathogenesis of atherosclerosis. Therapy with a reductase inhibitor of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) ("statin") produces significant alterations in various SMC functions. The objectives of the present study were to determine whether pitavastatin, a new chemically synthesized and powerful statin, can affect angiotensin II (Ang II)- and platelet-derived growth factor (PDGF)-induced migration and proliferation of cultured rat vascular SMCs. The effect of pitavastatin on cell viability was also examined in these cells. Migration was evaluated by the Boyden's chamber method using microchemotaxis chambers. As expected, Ang II and PDGF BB potently stimulated cell migration in a concentration-dependent manner. Pitavastatin significantly inhibited Ang II (10(-6) mol/l)-induced migration at the concentrations of 10(-8) and 10(-7) mol/l. Pitavastatin also inhibited PDGF BB (1 ng/ml)-induced migration at concentrations between 10(-9) and 10(-8) mol/l in a relatively concentration-dependent manner. This statin modestly but significantly inhibited Ang II (10(-6) mol/l)- and PDGF BB (1 ng/ml)-induced DNA synthesis at concentrations between 10(-9) and 10(-7) mol/l. In addition, pitavastatin clearly inhibited Ang II (10(-6) mol/l)- and PDGF BB (1 ng/ml)-induced increases of cell number at concentrations between 10(-9) and 10(-7) mol/l. Pitavastatin did not affect lactate dehydrogenase release from these cells at the concentrations used in this experiment. In a trypan blue exclusion test, dead cells stained with trypan blue were not found 24 h after treatment with 10(-9), 10(-8) or 10(-7) mol/l of pitavastatin. These findings suggest that pitavastatin suppresses the migration and proliferation stimulated by Ang II and PDGF BB without affecting cell viability. Pitavastatin may exert an anti-atherogenic effect, in part, through these mechanisms.

Inhibition of Migration and Proliferation of Rat Vascular Smooth Muscle Cells by a New HMG-CoA Reductase Inhibitor, Pitavastatin