title: Regulation of endothelial function by mitochondrial reactive oxygen species.
abstract: Mitochondria are well known for their central roles in ATP production, calcium homeostasis, and heme and steroid biosynthesis. However, mitochondrial reactive oxygen species (ROS), including superoxide and hydrogen peroxide, once thought to be toxic byproducts of mitochondrial physiologic activities, have recently been recognized as important cell-signaling molecules in the vascular endothelium, where their production, conversion, and destruction are highly regulated. Mitochondrial reactive oxygen species appear to regulate important vascular homeostatic functions under basal conditions in a variety of vascular beds, where, in particular, they contribute to endothelium-dependent vasodilation. On exposure to cardiovascular risk factors, endothelial mitochondria produce excessive ROS in concert with other cellular ROS sources. Mitochondrial ROS, in this setting, act as important signaling molecules activating prothrombotic and proinflammatory pathways in the vascular endothelium, a process that initially manifests itself as endothelial dysfunction and, if persistent, may lead to the development of atherosclerotic plaques. This review concentrates on emerging appreciation of the importance of mitochondrial ROS as cell-signaling molecules in the vascular endothelium under both physiologic and pathophysiologic conditions. Future potential avenues of research in this field also are discussed.
authors.affiliation: Department of Medicine, Cardiovascular Medicine Division and Department of Pharmacology, Medical College of Wisconsin , Milwaukee, Wisconsin.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Widlansky
authors.forename: David D
authors.initials: DD
authors.lastname: Gutterman
mesh_terms: D002118:Calcium / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D010544:Peroxidases / Q000378:metabolism; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*
chemical_list: D045462:Endothelium-Dependent Relaxing Factors; D013481:Superoxides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D010544:Peroxidases; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D002118:Calcium