Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is now clear that the availability of different metabolic substrates can have a profound influence on the extent of damage incurred during episodes of cardiac ischaemia, and on cardiac functional recovery on reperfusion following ischaemia. In particular, increases in fatty acid availability and oxidation, compared to glucose oxidation, under such conditions leads to a worsening of outcome. Therefore metabolic interventions aimed at enhancing glucose utilisation and pyruvate oxidation at the expense of fatty acid oxidation is a valid therapeutic approach to the treatment of myocardial ischaemia. In particular, the development of agents which will promote full glucose oxidation as opposed to glycolysis alone, offer clear advantages. This can be accomplished by different means, including direct or indirect inhibition of CPT-I or inhibition of fatty acid beta-oxidation, or by direct or indirect activation of PDH. It is not yet clear which of these approaches offers the best treatment of cardiac ischaemia. To date, trimetazidine and carnitine have received limited approval in Europe for the treatment of angina; large scale clinical trials with the other agents mentioned above have not been completed. The increasing availability of agents affecting these specific sites, and the increasingly sophisticated techniques for assessing myocardial metabolism, should allow elucidation of the optimum metabolic targets and development of novel pharmacological agents for the treatment of ischaemic heart disease.
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PMID:Regulation of myocardial carbohydrate metabolism under normal and ischaemic conditions. Potential for pharmacological interventions. 907 87

The effects of diabetes on myocardial metabolism are complex in that they are tied to the systemic metabolic abnormalities of the disease (hyperglycemia and elevated levels of free fatty acid and ketone bodies), and changes in cardiomyocyte phenotype (e.g., down-regulation of glucose transporters and PDH activity). The cardiac adaptations appear to be driven by the severity of the systemic abnormalities of the disease. The diabetes-induced changes in the plasma milieu and cardiac phenotype both cause impaired glycolysis, pyruvate oxidation, and lactate uptake, and a greater dependency on fatty acids as a source of acetyl CoA. Studies in isolated hearts suggest that therapies aimed at decreasing fatty acid oxidation, or directly stimulating pyruvate oxidation would be of benefit to the diabetic heart during and following myocardial ischemia.
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PMID:Regulation of energy substrate metabolism in the diabetic heart. 921 69

Xuesaitong injection (XST), which mainly consists of Panax notoginseng saponins, has been widely used for treating cardio-cerebral vascular diseases. However, the underlying mechanisms of XST associated with its cardioprotective effects are still unclear. To identify the potential target proteins of XST, two-dimensional gel electrophoresis (2-DE)-based proteomics was utilized to analyze the protein profile of myocardium in rats with myocardial ischemia/reperfusion (I/R) injury. The differentially expressed proteins were identified by matrix assisted laser desorption/ionization time-of-flight mass spectrometry. It is interesting that XST can alter the expression of 7 proteins, including pyruvate dehydrogenase E1 alpha (PDHA1), hydroxyacyl-coenzyme A dehydrogenase (HADHA), peroxiredoxin 3 (PRX3), gamma-enolase, acetyl-coenzyme A acyltransferase 2 (ACAA2), etc. Functional analysis revealed that those proteins were chiefly related to cardiac energy metabolism and oxidative stress. The cardioprotective effects of XST were further validated in H9c2 cardiac muscle cells with hypoxia/reoxygenation injury. We found that XST can promote the activity of PDH, an important enzyme related to the TCA cycle, as well as increase the intracellular content of acetyl-CoA and ATP. Moreover, XST also attenuated intracellular MDA release in H2O2-injured cardiac cells. This is the first study on the proteomic expression of XST-treated myocardium with I/R injury to reveal that the cardioprotective effects of XST may be attributed to the PDH-mediated restoration of aerobic glucose oxidation.
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PMID:Proteomic analysis reveals Xuesaitong injection attenuates myocardial ischemia/reperfusion injury by elevating pyruvate dehydrogenase-mediated aerobic metabolism. 2863 66

Myocardial ischemia is a condition with insufficient oxygen supporting the heart tissues, which may result from myocardial infarction or trauma-induced hemorrhagic shock. In order to develop better preventive and therapeutic strategies for myocardial ischemic damage, it is important that we understand the mechanisms underlying this type of injury. Mitochondrial-derived vesicles (MDVs) have been proposed as a novel player in maintaining mitochondrial quality control. This study aimed to investigate the role and possible mechanisms of MDVs in ischemia/hypoxia-induced myocardial apoptosis. H9C2 cardiomyocytes were used for the cellular experiments. A 40% fixed blood volume hemorrhagic shock rat model was used to construct the acute general ischemic models. MDVs were detected using immunofluorescence staining with PDH and TOM20. Exogenous MDVs were reconstituted in vitro from isolated mitochondria under different hypoxic conditions. The results demonstrate that MDV production was negatively correlated with cardiomyocyte apoptosis under hypoxic conditions; exogenous MDVs inhibited hypoxia-induced cardiomyocyte apoptosis; and MDV-mediated protection against hypoxia-induced cardiomyocyte apoptosis was accomplished via Bcl-2 interactions in the mitochondrial pathway. This study provides evidence that MDVs protect cardiomyocytes against hypoxic damage by inhibiting mitochondrial apoptosis. Our study used a novel approach that expands our understanding of MDVs and highlights that MDVs may be part of the endogenous response to hypoxia designed to mitigate damage. Strategies that stimulate cardiomyocytes to produce cargo-specific MDVs, including Bcl-2 containing MDVs, could theoretically be helpful in treating ischemic/hypoxic myocardial injury.
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PMID:Mitochondrial-Derived Vesicles Protect Cardiomyocytes Against Hypoxic Damage. 3242 51