title: Oxidative-nitrosative stress as a contributing factor to cardiovascular disease in subjects with diabetes.
abstract: In diabetes, clear evidence has emerged for the presence of oxidative-nitrosative stress, which may be a consequence of a glucose-mediated imbalance of systemic antioxidant buffering capacity, coupled with increased production of free radical species. Although multiple metabolic pathways have been identified, which may contribute to oxidative stress in diabetes, the principal pathogenetic pathways and their key down-stream targets remain to be established. Evidence links oxidative stress in particular, to elevations of postprandial glucose and lipids, which also have recently emerged as major risk factors for cardiovascular events. Indeed, considerable evidence suggests that increased oxidative stress in diabetes may play an important role in the development or progression of cardiovascular disease by a number of different mechanisms, including alterations of cardiovascular sympathetic nervous system tone and integrity, elevation of acute phase reactants, disruption of endothelial function and facilitation of myocardial injury. Despite the disappointments of recent large scale clinical trials evaluating the efficacy of antioxidants in cardiovascular disease, many therapeutic agents which have been used successfully in diabetic subjects at high risk for cardiovascular disease have a mechanism of action which includes an antioxidant capacity. Therefore, incorporating an antioxidant action in future therapeutic approaches to combat cardiovascular disease complicating diabetes, appears to remain justified and warrants further evaluation.
authors: Department of Medicine, Division of Medical Sciences, The Medical School, The University of Birmingham, Edgbaston, UK. m.j.stevens@bham.ac.uk
authors: Martin J
authors: MJ
authors: Stevens
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D048909:Diabetes Complications / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D015228:Hypertriglyceridemia / Q000378:metabolism; D018384:Oxidative Stress; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D014409:Tumor Necrosis Factor-alpha