ANTI-ANGIOGENESIS AND STATINS

The results of some clinical studies suggest that HMG-CoA reductase inhibitors, or statins, have cardioprotective effects that are independent of their lipid lowering effects. One of the most widely studied pleiotropic effects of statins is their ability to modify endothelial function and to modulate angiogenesis. Statins exercise a biphasic effect on angiogenesis, depending on the dose: at low concentrations they promote angiogenesis (pro-angiogenic effect) while at higher concentrations they inhibit it (anti-angiogenic effect). Although some of the potential anti-angiogenic effects could be derived from their anti-inflammatory activity, statins can inhibit key angiogenic mechanisms. The anti-angiogenic effects are a consequence of the reduction of isoprenylation of key proteins (i.e. RhoA), which intervene in signaling pathways that regulate the migration, proliferation and organizations of the cellular cytoskeleton. Currently, the real impact of the anti-angiogenic potential of statins on arteriosclerosis and on other diseases, such as cancer, in which angiogenesis is an important physiopathological component is unknown. Indeed, the results of some clinical studies suggest that these drugs could reduce the incidence of cancer. However, studies specifically designed to determine whether the anti-angiogenic activity of statins is important in arteriosclerosis and whether it can influence the growth and propagation of tumors are required.