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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    • "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.
    06/2015; 2015:1-9. DOI:10.1155/2015/515437
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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.
    Journal of Diabetes Research 04/2015; 2015. DOI:10.1155/2015/656795 · 2.16 Impact Factor
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    • "Nevertheless, it cannot be ignored that ISO did produce a trend toward higher MVO 2 in control muscles, an effect that may be due to mild mitochondrial uncoupling (Ljubkovic et al., 2007). In diabetic muscles, baseline force development and iCa were lower than those of control muscles, but MVO 2 was unchanged, indicating that diabetic muscles are less efficient, which is consistent with increased mitochondrial uncoupling (Bugger and Abel, 2010). Unlike in control muscles, in diabetic muscles, ISO attenuated mitochondrial respiration, as proven by reduced MVO 2 (Fig. 4) via increased oxidative stress (Bhatt et al., 2012). "

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