The emerging role of cardiovascular risk factor-inducedmitochondrial dysfunction in atherogenesis

摘要

An important role in atherogenesis is played by oxidative stress, which may be induced by commonrisk factors. Mitochondria are both sources and targets of reactive oxygen species, and there isgrowing evidence that mitochondrial dysfunction may be a relevant intermediate mechanism bywhich cardiovascular risk factors lead to the formation of vascular lesions. Mitochondrial DNA isprobably the most sensitive cellular target of reactive oxygen species. Damage to mitochondrialDNA correlates with the extent of atherosclerosis. Several cardiovascular risk factors aredemonstrated causes of mitochondrial damage. Oxidized low density lipoprotein andhyperglycemia may induce the production of reactive oxygen species in mitochondria ofmacrophages and endothelial cells. Conversely, reactive oxygen species may favor the developmentof type 2 diabetes mellitus, mainly through the induction of insulin resistance. Similarly - in additionto being a cause of endothelial dysfunction, reactive oxygen species and subsequent mitochondrialdysfunction - hypertension may develop in the presence of mitochondrial DNA mutations. Finally,other risk factors, such as aging, hyperhomocysteinemia and cigarette smoking, are also associatedwith mitochondrial damage and an increased production of free radicals. So far clinical studies havebeen unable to demonstrate that antioxidants have any effect on human atherogenesis.Mitochondrial targeted antioxidants might provide more significant results.