title: Oxidative stress and diabetic cardiovascular disorders: roles of mitochondria and NADPH oxidase.
abstract: Cardiovascular diseases are the predominant cause of death in patients with diabetes mellitus. Underlying mechanism for the susceptibility of diabetic patients to cardiovascular diseases remains unclear. Elevated oxidative stress was detected in diabetic patients and in animal models of diabetes. Hyperglycemia, oxidatively modified atherogenic lipoproteins, and advanced glycation end products are linked to oxidative stress in diabetes. Mitochondria are one of major sources of reactive oxygen species (ROS) in cells. Mitochondrial dysfunction increases electron leak and the generation of ROS from the mitochondrial respiratory chain (MRC). High levels of glucose and lipids impair the activities of MRC complex enzymes. NADPH oxidase (NOX) generates superoxide from NADPH in cells. Increased NOX activity was detected in diabetic patients. Hyperglycemia and hyperlipidemia increased the expression of NOX in vascular endothelial cells. Accumulated lines of evidence indicate that oxidative stress induced by excessive ROS production is linked to many processes associated with diabetic cardiovascular complications. Overproduction of ROS resulting from mitochondrial dysfunction or NOX activation is associated with uncoupling of endothelial nitric oxide synthase, which leads to reduced production of nitric oxide and endothelial-dependent vasodilation. Gene silence or inhibitor of NOX reduced oxidized or glycated LDL-induced expression of plasminogen activator inhibitor-1 in endothelial cells. Statins, hypoglycemic agents, and exercise may reduce oxidative stress in diabetic patients through the reduction of NOX activity or the improvement of mitochondrial function, which may prevent or postpone the development of cardiovascular complications.
authors.affiliation: Department of Internal Medicine, University of Manitoba, 835-715 McDermot Avenue, Winnipeg MB R3E 3P4, Canada. gshen@ms.umanitoba.ca
authors.forename: Garry X
authors.initials: GX
authors.lastname: Shen
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000150:complications / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D019255:NADPH Oxidases / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D019255:NADPH Oxidases