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.

Cobalt-Protoporphyrin Improves Heart Function by Blunting Oxidative Stress and Restoring NO Synthase Equilibrium in an Animal Model of Experimental Diabetes

“…The mechanisms responsible for the effects of hyperglycemia and diabetes on myocardial function and on coronary macro- and micro-vasculature are the object of intensive investigation. Among several putative mechanisms, the role of the reactive oxygen (ROS) and reactive nitrogen species (RNS) has been studied in a number of experimental models of diabetes (Stevens, 2005). Oxidative stress associated with deficient antioxidant systems has been reported to play a critical role in subcellular remodeling, calcium handling, and subsequent diabetic cardiomyopathy (Haidara et al, 2006).…”

3-Bromo-7-nitroindazole attenuates brain ischemic injury in diabetic stroke via inhibition of endoplasmic reticulum stress pathway involving CHOP

“…We have recently reported that diabetes exacerbates ischemic brain injury by augmenting ER stress and apoptosis associated with enhanced CHOP induction in rats (Srinivasan and Sharma, 2011). Diabetes has been further postulated to induce oxidative/nitrosative stress in brain and also implicated in various micro-and macrovascular complications (Ergul et al, 2009;Mastrocola et al, 2005;Stevens, 2005). In addition, hyperglycemia augments ischemic brain injury via inducing glutamate excitotoxicity and NO-mediated toxicity following I/R (Wei and Quast, 1998).…”

Apolipoprotein A‐I mimetic peptide L‐4F prevents myocardial and coronary dysfunction in diabetic mice

“…Besides the direct effects of impaired insulin pathways as well as hyperglycaemia on myocardial metabolism, other relevant mechanisms include enhanced oxidative stress (Ceriello, 2002; Stevens, 2005), low oxygen availability secondary to coronary endothelial/vascular damage (Rask-Madsen and King 2007) and increased susceptibility to ischemia (Rytter, 1985; Hink, 2001; Cai, 2002). Relevant contributing mechanisms involve the endocrine function of the adipose tissue and the inflammatory pathway (Berg, 2005).…”