Statin therapy and angiogenesis

Clinical studies suggested that 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy has an additional cardiovascular protective activity that may function independently of the ability of statins to lower serum cholesterol. This paper reviews the available data on these effects and discusses the potential intracellular mechanisms involved.

Experimental studies have clearly shown that statins protect against ischaemia-reperfusion injury of the heart, and exert pro-angiogenic effects by stimulating the growth of new blood vessels in ischaemic limbs of normocholesterolemic animals. The mechanisms underlying these serum lipid-independent statin effects are not completely understood, but there is increasing evidence that statins 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. In contrast to these data, it has also been reported that higher doses of statins can inhibit endothelial cell migration and angiogenesis.

Statins have biphasic potential either to promote or inhibit angiogenesis. Low statin doses induce a pro-angiogenic effect through Akt activation and increase nitric oxide production, whereas high statin doses may decrease protein prenylation and inhibit cell growth. Notwithstanding, the clinical relevance of these serum lipid-independent effects is not fully understood. Further studies on the actions of statins on endothelial cells may lead to the identification of new pharmacological targets for the control of angiogenesis.