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)

Tracer techniques have provided new insight in cardiology by allowing noninvasive studies of myocardial perfusion, function, metabolism, and, more recently, ligand-receptor interaction. Positron emission tomography allows accurate quantification and the use of natural substrates labelled with 11C, 13N, or 15O. Myocardial metabolism is complex and utilizes a number of substrates, primarily fatty acids. Fatty acids utilization can be studied with 11C palmitate, while 11C acetate more selectively traces TCA cycle activity and reflects myocardial oxygen utilization. Glucose uptake can be traced using 18F deoxyglucose, a glucose analog that is a substrate for hexokinase but is not further metabolized. Flow and oxidative glucose metabolism are usually coupled, and thereby the uptake of FDG and perfusion tracers are usually similar. In myocardial ischemia, however, glucose utilization can persist due to anaerobic glycolysis, and its uptake is frequently enhanced. Clinical applications of the use of metabolic studies in patients with ischemic heart disease are presented.
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PMID:Imaging of myocardial metabolism by positron emission tomography. 209 80

Undoubtedly, metabonomics can reveal the comprehensive efficacies of traditional Chinese medicine (TCM) formulae and its complex mechanism at the molecular biological level. In this study, an attempt was made to address the pretreatment effect of a TCM formula. In this case, as a critical point, we should first know how to really reflect the various endogenous metabolites in a disease status before a TCM formula is employed in a therapeutic procedure. Here, we explored an approach that combined high resolution LTQ-Orbitrap mass spectrometry with a spike-in method to characterize endogenous metabolites in acute myocardial ischemia (AMI) rats. As a result, 19 potential biomarkers in rat plasma were identified and 10 related disturbed pathways were perturbed in the early stages of AMI development. Subsequently, the metabonomics method was applied to investigate the pretreatment effect of the TCM formula named the Danqi Tongmai tablet (DQTM). The results revealed that the DQTM pretreatment could reduce the AMI injury and partially regulate the perturbed TCA cycle and amino and nucleotide metabolism, which were presumable related to energy metabolism and myocardial cells apoptosis/necrosis. In conclusion, UHPLC-LTQ-Orbitrap MS combined with a spike-in method were successfully applied to the metabonomics analysis of DQTM, which demonstrated that not only a comprehensive metabolic profile in the early stages of AMI development was achieved, but also that the underlying holistic efficacies were assessed and it was helpful to understand the possible mechanism of pretreatment with DQTM.
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PMID:UHPLC-LTQ-Orbitrap MS combined with spike-in method for plasma metabonomics analysis of acute myocardial ischemia rats and pretreatment effect of Danqi Tongmai tablet. 2541 80

Mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) is a common end effector of many protective stimuli in myocardial ischemia-reperfusion injury (MIRI). However, the specific molecular mechanism underlying its myocardial protective effect is not well elucidated. We characterized an anoxia/reoxygenation (A/R) model using freshly isolated adult rat cardiomyocytes. MitoK(ATP) status was interfered with its specific opener diazoxide (DZ) or blocker 5-hydroxydecanote (5-HD). Digital gene expression (DGE) and bioinformatic analysis were deployed. Three energy metabolism related genes (MT-ND6, Idh2, and Acadl) were upregulated when mitoK(ATP) opened. In addition, as many as 20 differentially expressed genes (DEGs) were significantly enriched in five energy homeostasis correlated pathways (PPAR, TCA cycle, fatty acid metabolism, and peroxisome). These findings indicated that mitoK(ATP) opening in MIRI resulted in energy mobilization, which was confirmed by measuring ATP content in cardiomyocytes. These causal outcomes could be a molecular mechanism of myocardial protection of mitoKATP and suggested that the mitoK(ATP) opening plays a physiologic role in triggering cardiomyocytes' energy homeostasis during MIRI. Strategies of modulating energy expenditure during myocardial ischemia-reperfusion may be promising approaches to reduce MIRI.
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PMID:Genome-Wide Expression Profiling of Anoxia/Reoxygenation in Rat Cardiomyocytes Uncovers the Role of MitoKATP in Energy Homeostasis. 2617 Nov 16

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

Sirtuin4 (Sirt4) is one of the mammalian homologues of Silent information regulator 2 (Sir2), which promotes the longevity of yeast, C. elegans, fruit flies and mice. Sirt4 is localized in the mitochondria, where it contributes to preventing the development of cancers and ischemic heart disease through regulating energy metabolism. The ADP-ribosylation of glutamate dehydrogenase (GDH), which is catalyzed by Sirt4, downregulates the TCA cycle. However, this reaction mechanism is obscure, because the structure of Sirt4 is unknown. We here constructed structural models of Sirt4 by homology modeling and threading, and docked nicotinamide adenine dinucleotide+ (NAD+) to Sirt4. In addition, a partial GDH structure was docked to the Sirt4-NAD+ complex model. In the ternary complex model of Sirt4-NAD+-GDH, the acetylated lysine 171 of GDH is located close to NAD+. This suggests a possible mechanism underlying the ADP-ribosylation at cysteine 172, which may occur through a transient intermediate with ADP-ribosylation at the acetylated lysine 171. These results may be useful in designing drugs for the treatment of cancers and ischemic heart disease.
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PMID:A ternary complex model of Sirtuin4-NAD+-Glutamate dehydrogenase. 2957 Oct 13

Previous studies have suggested that exposure to ionizing radiation increases the risk of ischemic heart disease (IHD). The data from the Mayak nuclear worker cohort have indicated enhanced risk for IHD incidence. The goal of this study was to elucidate molecular mechanisms of radiation-induced IHD by integrating proteomics data with a transcriptomics study on post mortem cardiac left ventricle samples from Mayak workers categorized in four radiation dose groups (0 Gy, < 100 mGy, 100-500 mGy, > 500 mGy). The proteomics data that were newly analysed here, originated from a label-free analysis of cardiac samples. The transcriptomics analysis was performed on a subset of these samples. Stepwise linear regression analyses were used to correct the age-dependent changes in protein expression, enabling the separation of proteins, the expression of which was dependent only on the radiation dose, age or both of these factors. Importantly, the majority of the proteins showed only dose-dependent expression changes. Hierarchical clustering of the proteome and transcriptome profiles confirmed the separation of control and high-dose samples. Restrictive (separate p-values) and integrative (combined p-value) approaches were used to investigate the enrichment of biological pathways. The integrative method proved superior in the validation of the key biological pathways found in the proteomics analysis, namely PPAR signalling, TCA cycle and glycolysis/gluconeogenesis. This study presents a novel, improved, and comprehensive statistical approach of analysing biological effects on a limited number of samples.
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PMID:Integrative multiomics study for validation of mechanisms in radiation-induced ischemic heart disease in Mayak workers. 3059 17