Oxidative stress in vascular disease and its pharmacological prevention

Cardiovascular risk factors lead to enhanced production of reactive oxygen species (ROS) generated by NADPH oxidase, xanthine oxidase (XO), the mitochondrial electron-transport chain (ETC), and dysfunctional endothelial nitric oxide synthase (eNOS). When the capacity of antioxidant defense systems [e.g., superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), heme oxygenase (HO), paraoxonase (PON)] is exceeded, this results in oxidative stress, which can promote atherogenesis. Therefore, pharmacological means to prevent oxidative stress are of major therapeutic interest. Some established drugs and novel therapeutic approaches can prevent oxidative stress and, presumably, vascular disease. These include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor type 1 (AT1 receptor) blockers (ARBs), statins, nebivolol, pentaerithrityl tetranitrate (PETN), resveratrol, and mitochondria-targeted antioxidants. Molecular mechanisms involved in the induction of oxidative stress under pathological conditions as well as pharmacological approaches (and their molecular mechanisms) are summarized in this review.