The pro- and antiangiogenic effects of statins.

Clinical studies indicate that 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) therapy has a cardiovascular protective activity that may result from an improvement in endothelial function. Experimental studies have shown that statins protect against ischaemia-reperfusion injury of the heart and stimulate the growth of new blood vessels in ischemic limbs of normocholesterolemic animals. The mechanisms underlying these serum lipid-independent effects of statins are not completely understood, but there is increasing evidence that they improve endothelial function through molecular mechanisms that mediate an increase in endothelium-derived nitric oxide. Recent research has revealed a link between statins and the serine/threonine protein kinase Akt that regulates multiple angiogenic processes in endothelial cells, including the generation of nitrous oxide. In contrast to these data, it has also been reported that higher doses of statins inhibit endothelial cell migration and angiogenesis. Thus, further studies on the actions of statins may lead to the identification of new pharmacological targets for the control of blood vessel growth.