Nitric oxide, oxidative excess, and vascular complications of diabetes mellitus.
The prevalence of diabetes mellitus is rising worldwide and has reached epidemic dimensions. Diabetes mellitus places patients at high cardiovascular risk. High blood glucose levels, altered insulin signaling, reactive oxygen species (ROS), inflammation, and protein kinase C activation might lead to a decrease in nitric oxide (NO) bioavailability. Diminished NO and enhanced oxidative stress play a central role in several pathophysiologic pathways, leading to vascular damage, such as endothelial dysfunction, vascular inflammation, atherosclerotic plaque formation and vulnerability, and promotion of a prothrombotic state. Possible sources of oxidative excess in diabetes are reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, uncoupled NO synthase, and the mitochondria. Advances in understanding the pathophysiologic mechanisms leading to vascular damage in diabetes will result in discovery of new therapeutic targets, which should help reduce cardiovascular risk in these patients.
Clinical Research Institute of Montreal, 110 Pine Avenue W, Montreal, Quebec, Canada H2W 1R7.
Dierk H
DH
Endemann
Ernesto L
EL
Schiffrin
D000818:Animals; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D014652:Vascular Diseases / Q000209:etiology / Q000503:physiopathology*
D009569:Nitric Oxide