Mitochondria in the diabetic heart

Department of Cardiology, University of Freiburg, Freiburg, Germany.
Cardiovascular Research (Impact Factor: 5.94). 11/2010; 88(2):229-40. DOI: 10.1093/cvr/cvq239
Source: PubMed


Diabetes mellitus increases the risk of developing cardiovascular diseases such as coronary artery disease and heart failure. Studies have shown that the heart failure risk is increased in diabetic patients even after adjusting for coronary artery disease and hypertension. Although the cause of this increased heart failure risk is multifactorial, increasing evidence suggests that derangements in cardiac energy metabolism play an important role. In particular, abnormalities in cardiomyocyte mitochondrial energetics appear to contribute substantially to the development of cardiac dysfunction in diabetes. This review will summarize these abnormalities in mitochondrial function and discuss potential underlying mechanisms.

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    • "As noted earlier, ROS-induced mitochondrial dysfunction is of particular interest in the development of HF[102,103]. While the mitochondrial respiratory chain (MRC) enzyme complexes consisting of mtDNA-encoded and nDNA-encoded subunits are required for mitochondrial oxidative phosphorylation, Ide et al. demonstrated in a canine model of tachyarrhythmia-induced HF that increased intra-mitochondrial ROS in the failing myocardium induces dysfunction in the adjacent mitochondrial membrane and mtDNA, resulting in impaired enzymatic activity of the MRC complex I. "
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    ABSTRACT: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM). DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD), cardiac hypertrophy, and heart failure (HF). HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS). ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease.
    Full-text · Article · Oct 2015 · International Journal of Molecular Sciences
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    • "Elucidation of the pathogenesis of diabetic cardiomyopathy is currently an active field of research. In particular, metabolic impairment and mitochondrial dysfunction have been systematically investigated in the past decades in both clinical and experimental settings (reviewed in [70] [71] [72] [73] [74]). We will further refer to the impairment of respiratory capacity and the subsequent redox imbalance in order to highlight commonalities with the aforementioned findings in HF. "
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    ABSTRACT: Oxidative stress is a pathomechanism causally linked to the progression of chronic cardiovascular diseases and diabetes. Mitochondria have emerged as the most relevant source of reactive oxygen species, the major culprit being classically considered the respiratory chain at the inner mitochondrial membrane. In the past decade, several experimental studies unequivocally demonstrated the contribution of monoamine oxidases (MAOs) at the outer mitochondrial membrane to the maladaptative ventricular hypertrophy and endothelial dysfunction. This paper addresses the contribution of mitochondrial dysfunction to the pathogenesis of heart failure and diabetes together with the mounting evidence for an emerging role of MAO inhibition as putative cardioprotective strategy in both conditions.
    Full-text · Article · Jun 2015
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    • "Energetic imbalance triggers defects of mitochondrial respiration and ROS overload in human diabetes. In both T1DM and T2DM, metabolic maladaptation contributes to ROS imbalance by affecting multiple enzymatic systems including NADH oxidase (NOX), endothelial NO synthase, and, mainly, the mitochondrial respiratory chain [68] [75]. In STZtreated rats, mitochondrial damage was evidenced by loss of membrane potential, increases in ROS production, and reduction in antioxidant glutathione [76] (Table 1). "
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    ABSTRACT: Diabetic cardiomyopathy entails a serious cardiac dysfunction induced by alterations in structure and contractility of the myocardium. This pathology is initiated by changes in energy substrates and occurs in the absence of atherothrombosis, hypertension, or other cardiomyopathies. Inflammation, hypertrophy, fibrosis, steatosis, and apoptosis in the myocardium have been studied in numerous diabetic experimental models in animals, mostly rodents. Type I and type II diabetes were induced by genetic manipulation, pancreatic toxins, and fat and sweet diets, and animals recapitulate the main features of human diabetes and related cardiomyopathy. In this review we update and discuss the main experimental models of diabetic cardiomyopathy, analysing the associated metabolic, structural, and functional abnormalities, and including current tools for detection of these responses. Also, novel experimental models based on genetic modifications of specific related genes have been discussed. The study of specific pathways or factors responsible for cardiac failures may be useful to design new pharmacological strategies for diabetic patients.
    Full-text · Article · Apr 2015 · Journal of Diabetes Research
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