The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals.

Recent studies suggest that statins can function to protect the vasculature in a manner that is independent of their lipid-lowering activity. We show here that statins rapidly activate the protein kinase Akt/PKB in endothelia l cells. Accordingly, simvastatin enhanced phosphorylation of the endogenou s Akt substrate endothelial nitric oxide synthase (eNOS), inhibited apoptos is and accelerated vascular structure formation in vitro in an Akt-dependen t manner. Similar to vascular endothelial growth factor (VEGF) treatment,bo th simvastatin administration and enhanced Akt signaling in the endothelium promoted angiogenesis in ischemic limbs of normocholesterolemic rabbits. T herefore, activation of Akt represents a mechanism that can account for som e of the beneficial side effects of statins, including the promotion of new blood vessel growth.