Anderson 2009 J Am Coll Cardiol
|Anderson EJ, Kypson AP, Rodriguez E, Anderson CA, Lehr EJ, Neufer PD (2009) Substrate-specific derangements in mitochondrial metabolism and redox balance in the atrium of the type 2 diabetic human heart. J Am Coll Cardiol 54:1891-8.|
Abstract: The aim of this study was to determine the impact of diabetes on oxidant balance and mitochondrial metabolism of carbohydrate- and lipid-based substrates in myocardium of type 2 diabetic patients. Background Heart failure represents a major cause of death among diabetic patients. It has been proposed that derangements in cardiac metabolism and oxidative stress may underlie the progression of this comorbidity, but scarce evidence exists in support of this mechanism in humans. Methods Mitochondrial oxygen (O2) consumption and hydrogen peroxide (H2O2) emission were measured in permeabilized myofibers prepared from samples of the right atrial appendage obtained from nondiabetic (n=13) and diabetic (n=11) patients undergoing nonemergent coronary artery bypass graft surgery. Results Mitochondria in atrial tissue of type 2 diabetic individuals show a sharply decreased capacity for glutamate and fatty acid-supported respiration, in addition to an increased content of myocardial triglycerides, as compared to nondiabetic patients. Furthermore, diabetic patients show an increased mitochondrial H2O2 emission during oxidation of carbohydrate- and lipid-based substrates, depleted glutathione, and evidence of persistent oxidative stress in their atrial tissue. Conclusions These findings are the first to directly investigate the effects of type 2 diabetes on a panoply of mitochondrial functions in the human myocardium using cellular and molecular approaches, and they show that mitochondria in diabetic human hearts have specific impairments in maximal capacity to oxidize fatty acids and glutamate, yet increased mitochondrial H2O2 emission, providing insight into the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of heart failure in diabetic patients.
• Keywords: Diabetic cardiomyopathy, Permeabilized muscle fiber from human atrial appendage biopsy, Permanent oxidative stresss, ROS production, HNE (hydroxynonenal)- and 3-nitrotyrosine–modified proteins, Fatty acids oxidation and Gluthatione
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, mt-Medicine Pathology: Aging;senescence, Diabetes Stress:Oxidative stress;RONS, Mitochondrial disease Organism: Human Tissue;cell: Heart Preparation: Permeabilized tissue Enzyme: Complex II;succinate dehydrogenase Regulation: Aerobic glycolysis, Substrate, Fatty acid Coupling state: OXPHOS, ET