title: Mitochondrial dysfunction, oxidative stress and diabetic cardiovascular disorders.
abstract: The prevalence of diabetes has been rapidly increasing in world-wide countries. The dominant cause of mortality in diabetic patients is cardiovascular complications. Mechanism for the susceptibility of diabetic patients to cardiovascular disorders remains unclear. Elevated oxidative stress was detected in diabetic patients or in animal models. Mitochondria are one of major sources of reactive oxygen species (ROS) in cells. Mitochondrial dysfunction and DNA mutations have been detected in diabetic patients. Diabetes-associated metabolic disorders, including hyperglycemia, hypertriglyceridemia, hypercholesterolemia, hypoalphalipoproteinemia, and increased levels of advanced glycation end products, glycated and oxidized lipoproteins, are associated with oxidative stress. Glycated or oxidized low density lipoproteins (LDL) impair the activities of mitochondrial respiratory chain complex enzymes in vascular endothelial cells (EC). Dysfunction in mitochondrial respiration may increase the formation of ROS in mitochondria. NADPH oxidase (NOX) generates ROS in cytosol. Increased NOX activity was detected in diabetic patients. Glycated and oxidized LDL increase the expression of NOX and ROS production in EC. Diabetes-associated metabolic disorders may lead to mitochondrial dysfunction, NOX activation and excess ROS production, which results in oxidative stress and promotes cardiovascular disorders in diabetic patients. Statins, metformin and anthocyanidins may help to attenuate oxidative stress in vasculature induced by diabetes-associated metabolic disorders.
authors.affiliation: Diabetes Research Group, University of Manitoba, Winnipeg, Canada. gshen@ms.umanitoba.ca
authors.forename: Garry X
authors.initials: GX
authors.lastname: Shen
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species