Diabetic cardiomyopathy: fact or fiction?

Francis, Gary S.

doi:10.1136/heart.85.3.247

Cited by 99 publications

(68 citation statements)

References 14 publications

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“…Diabetic cardiomyopathy is characterized by a reduction in cardiac mass over time, myocardial hypertrophy, and interstitial and perivascular fibrosis at late phase (1)(2)(3)(4)(5). Because myocytes rarely proliferate in adult cardiac muscles, the loss of cardiac muscle cells would eventually lead to compromised cardiac function.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that hyperglycemia as an independent risk factor directly causes cardiac damage, lending to diabetic cardiomyopathy (1)(2)(3)(4). However, mechanisms for the pathogenesis remain unclear (1)(2)(3)(4)(5). Diabetic hearts, including streptozotocin (STZ)-induced diabetic animal models, display a reduction in cardiac mass over time, myocardial hypertrophy, and interstitial and perivascular fibrosis at late phase (5,6).…”

mentioning

confidence: 99%

“…However, mechanisms for the pathogenesis remain unclear (1)(2)(3)(4)(5). Diabetic hearts, including streptozotocin (STZ)-induced diabetic animal models, display a reduction in cardiac mass over time, myocardial hypertrophy, and interstitial and perivascular fibrosis at late phase (5,6). These late-phase changes are believed to result from early responses of myocardium to suddenly increased glucose levels (1,6 -8).…”

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confidence: 99%

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Hyperglycemia-Induced Apoptosis in Mouse Myocardium

et al. 2002

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Diabetic cardiomyopathy is related directly to hyperglycemia. Cell death such as apoptosis plays a critical role in cardiac pathogenesis. Whether hyperglycemia induces myocardial apoptosis, leading to diabetic cardiomyopathy, remains unclear. We tested the hypothesis that apoptotic cell death occurs in the diabetic myocardium through mitochondrial cytochrome c-mediated caspase-3 activation pathway. Diabetic mice produced by streptozotocin and H9c2 cardiac myoblast cells exposed to high levels of glucose were used. In the hearts of diabetic mice, apoptotic cell death occurred as detected by terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) assay. Correspondingly, caspase-3 activation as determined by enzymatic assay and mitochondrial cytochrome c release detected by Western blotting analysis were observed. Supplementation of insulin inhibited diabetesinduced myocardial apoptosis as well as suppressed hyperglycemia. To explore whether apoptosis in diabetic hearts is related directly to hyperglycemia, we exposed cardiac myoblast H9c2 cells to high levels of glucose (22 and 33 mmol/l) in cultures. Apoptotic cell death was detected by TUNEL assay and DAPI nuclear staining. Caspase-3 activation with a concomitant mitochondrial cytochrome c release was also observed. Apoptosis or activation of caspase-3 was not observed in the cultures exposed to the same concentrations of mannitol. Inhibition of caspase-3 with a specific inhibitor, Ac-DEVD-cmk, suppressed apoptosis induced by high levels of glucose. In addition, reactive oxygen species (ROS) generation was detected in the cells exposed to high levels of glucose. These results suggest that hyperglycemia directly induces apoptotic cell death in the myocardium in vivo. Hyperglycemiainduced myocardial apoptosis is mediated, at least in part, by activation of the cytochrome c-activated caspase-3 pathway, which may be triggered by ROS derived from high levels of glucose.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Hyperglycemia-Induced Apoptosis in Mouse Myocardium

et al. 2002

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“…Several factors have been reported to be involved in the pathogenesis of this disease, including hyperglycemia, insulin resistance and oxidative stress-induced insults (3,4,5). Among these factors, hyperglycemia is considered one of the most important factors in the onset of diabetic cardiomyopathy (4,6).…”

Section: Introductionmentioning

confidence: 99%

Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways

Wang

Chen

et al. 2013

International Journal of Molecular Medicine

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Abstract. Hyperglycemia is a risk factor for the development of diabetic cardiovascular complications, which are associated with the activation of the mitogen-activated protein kinase (MAPK) signaling pathway. In this study, we demonstrate the inhibitory effects of exogenous hydrogen sulfide (H 2 S) on the activation of the MAPK pathway. The aim of the present study was to determine whether exogenous H 2 S prevents high glucose (HG)-induced injury by inhibiting the activation of the p38 MAPK and extracellular signal-regulated kinase (ERK)1/2 (members of MAPK) pathways in cardiomyoblasts (H9c2 cells). The findings of the present study demonstrated that the treatment of H9c2 cells with HG (35 mM glucose) for 24 h not only significantly induced injury, including cytotoxicity, apoptosis, overproduction of reactive oxygen species (ROS) and the loss of mitochondrial membrane potential (MMP), but also upregulated the expression levels of phosphorylated (p)-p38 MAPK and p-ERK1/2. The increased expression levels of p-p38 MAPK and p-ERK1/2 were markedly reduced by pre-treatment of the H9c2 cells with 400 µM sodium hydrogen sulfide (NaHS; a donor of H 2 S) prior to exposure to 35 mM glucose. Importantly, pre-treatment of the cells with 400 µM NaHS or 3 µM SB203580 (a selective inhibitor of p38 MAPK) or 15 µM U0126 (a selective inhibitor of ERK1/2) attenuated the HG-induced cardiomyocyte injury, leading to an increase in cell viability and a decrease in the number of apoptotic cells, preventing ROS generation, as well as the loss of MMP. In addition, pre-treatment of the cells with 1,000 µM N-acetyl-L-cysteine (a ROS scavenger) prior to exposure to HG ameliorated the HG-induced cytotoxicity. Taken together, the data from the present study demonstrate for the first time, to our knowledge, that exogenous H 2 S exerts a protective effect against HG-induced injury by inhibiting the activation of the p38 MAPK and ERK1/2 pathways and preventing oxidative stress in H9c2 cells.

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“…Diabetic cardiomyopathy, a complication causing heart failure, can occur independently of vascular complications, such as coronary artery disease and hypertension, thus representing a distinct disease process (Francis, 2001;Murarka and Movahed, 2010). The mechanism by which diabetes causes cardiomyopathy remains largely unclear.…”

Section: Introductionmentioning

confidence: 99%

Redox Regulation by Nuclear Factor Erythroid 2-Related Factor 2: Gatekeeping for the Basal and Diabetes-Induced Expression of Thioredoxin-Interacting Protein

2012

Mol Pharmacol

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Diabetic cardiomyopathy: fact or fiction?

Cited by 99 publications

References 14 publications

Hyperglycemia-Induced Apoptosis in Mouse Myocardium

Hyperglycemia-Induced Apoptosis in Mouse Myocardium

Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways

Redox Regulation by Nuclear Factor Erythroid 2-Related Factor 2: Gatekeeping for the Basal and Diabetes-Induced Expression of Thioredoxin-Interacting Protein

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