Role of peroxynitrite in the pathogenesis of cardiovascular complications of diabetes.
Hyperglycemic episodes, which complicate even well-controlled cases of diabetes, lead to increased polyol pathway flux, activation of protein kinase C and accelerated non-enzymatic formation of advanced glycation end products. Many of these pathways become activated in response to the production of superoxide anion. Superoxide can interact with nitric oxide, forming the potent cytotoxin peroxynitrite. Peroxynitrite attacks various biomolecules in the vascular endothelium, vascular smooth muscle and myocardium, eventually leading to cardiovascular dysfunction via multiple mechanisms. This review focuses on emerging evidence suggesting that peroxynitrite plays a key role in the pathogenesis of the cardiovascular complications of diabetes, which underlie the development and progression of diabetic retinopathy, neuropathy and nephropathy.
National Institutes of Health, NIAAA, Laboratory of Physiologic Studies, 5625 Fishers Lane MSC 9413, Bethesda, Maryland 20852, USA. pacher@mail.nih.gov
Pál
P
Pacher
Csaba
C
Szabó
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology; D009202:Cardiomyopathies / Q000209:etiology*; D048909:Diabetes Complications / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D030421:Peroxynitrous Acid / Q000009:adverse effects*
D030421:Peroxynitrous Acid