Abstract
William Osler stated that “A man is as old as his arteries.” Now, it has been known that attenuation of the production of reactive oxygen species and inhibition of inflammatory pathways play a central role in the anti-aging therapy for vasculature. Dysfunction of endothelial cells (EC) has been known to promote abnormal vascular growth such as that in atherosclerosis and arteriosclerosis and postulated as an initial trigger of the progression of atherosclerosis in patients with diabetes mellitus, hypertension and hyperlipidemia. We and others have previously demonstrated high D-glucose directly induced apoptosis through activation of the bax-caspase proteases pathway in human EC. Although it has been known for years that vascular cells can release a large amount ROS, including superoxide, hydrogen peroxide, and nitric oxide, the role of oxidative stress in atherogenesis has received increasing attention in recent years. Recent works strongly suggest that NADPH oxidase is a major source of superoxide in cardiovascular cells oxidative stress can be involved in the process of endothelial dysfunction. From a view of these molecular mechanisms, HMG-CoA reductase inhibitor (stains) might inhibit the NADPH oxidase activation through inhibition of Rac activity and finally prevent the increase in ROS production in diabetes. Actually, recent clinical trial suggests that statins prevent several vascular events in patients with type 2 diabetes without high concentration of LDL-cholesterol. This pleiotropic effect of statins can improve endothelial dysfunction through Nitric Oxide production and/or anti-oxidant effect in diabetes patients.
