Overview of the Components of Cardiac Metabolism

Hausner, Elizabeth; Elmore, Susan A.; Yang, Xi

doi:10.1124/dmd.119.086611

Cited by 25 publications

(17 citation statements)

References 220 publications

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“…ABC transporters are a series of ATP-dependent transport enzymes, which can transport multiple endogenous compounds including amino acids, ions, and nucleotides. Researchers have found that ABC transporters are involved in the homeostasis of the heart [29]. We found that the transport of amino acids (e.g., glutamate) was altered after MI.…”

Section: Plos Onementioning

confidence: 71%

Proteomic and metabolomic characterization of cardiac tissue in acute myocardial ischemia injury rats

Bai

Sun

et al. 2020

PLoS ONE

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The pathological process and mechanism of myocardial ischemia (MI) is very complicated, and remains unclear. An integrated proteomic-metabolomics analysis was applied to comprehensively understand the pathological changes and mechanism of MI. Male Sprague-Dawley rats were randomly divided into a mock surgery (MS) group and an MI group. The MI model was made by ligating the left anterior descending coronary artery, twenty-four hours after which, echocardiography was employed to assess left ventricular (LV) function variables. Blood samples and left ventricular tissues were collected for ELISA, metabolomics and proteomics analysis. The results showed that LV function, including ejection fraction (EF) and fractional shortening (FS), was significantly reduced and the level of cTnT in the serum increased after MI. iTRAQ proteomics showed that a total of 169 proteins were altered including 52 and 117 proteins with increased and decreased expression, respectively, which were mainly involved in the following activities: complement and coagulation cascades, tight junction, regulation of actin cytoskeleton, MAPK signaling pathway, endocytosis, NOD-like receptor signaling pathway, as well as phagosome coupled with vitamin digestion and absorption. Altered metabolomic profiling of this transition was mostly enriched in pathways including ABC transporters, glycerophospholipid metabolism, protein digestion and absorption and aminoacyl-tRNA biosynthesis. The integrated metabolomics and proteomics analysis indicated that myocardial injury after MI is closely related to several metabolic pathways, especially energy metabolism, amino acid metabolism, vascular smooth muscle contraction, gap junction and neuroactive ligand-receptor interaction. These findings may contribute to understanding the mechanism of MI and have implication for new therapeutic targets.

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Section: Plos Onementioning

confidence: 71%

Proteomic and metabolomic characterization of cardiac tissue in acute myocardial ischemia injury rats

Bai

Sun

et al. 2020

PLoS ONE

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“…ABC transporters are a family of ATP-dependent transporters that can transport a variety of endogenous compounds, including amino acids, ions, nucleotides, lipids, and peptides, across the cell membrane. Researchers have found that ABC transporters are altered after MI and are involved in cardiac homeostasis [ 33 , 34 ], which constitute future research directions regarding the cardioprotective effect of proline metabolism.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Analysis of the Ameliorative Effect of Enhanced Proline Metabolism on Hypoxia-Induced Injury in Cardiomyocytes

Wang

Xue

Hua

et al. 2020

Oxidative Medicine and Cellular Longevity

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Background. Coronary heart disease is currently the leading cause of death in humans. Its poor prognosis and high mortality are associated with myocardial ischemia, which leads to metabolic disorder-related cardiomyocyte apoptosis and reactive oxygen species (ROS) production. Previous cardiovascular metabolomics studies in humans and mice have shown that proline metabolism is severely altered after cardiomyocyte hypoxia. Proline dehydrogenase (PRODH) is located on the inner mitochondrial membrane and is an enzyme that catalyzes the first step of proline catabolism, which plays an important role in improving the cellular redox state. In vitro oxygen-glucose deprivation can mimic in vivo myocardial ischemic injury. This study is aimed at investigating whether enhancing proline metabolism by overexpressing PRODH can ameliorate hypoxia-induced injury in cardiomyocytes and to reveal the related altered metabolites and mechanistic pathway via untargeted metabolomics analysis. Methods and Results. First, through public database analysis and RT-qPCR and western blot analyses in a cardiomyocyte hypoxia model, we found that the expression of the proline-degrading enzyme PRODH was downregulated after myocardial infarction and hypoxia exposure. Second, LDH assays, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), DHE staining, flow cytometric apoptosis analysis with DCFH and Annexin V-FITC/PI, and western blot analysis were used to assess the injury level in cardiomyocytes. Enhanced proline metabolism induced by PRODH overexpression reduced the levels of reactive oxidative stress and apoptosis, whereas PRODH knockdown had the opposite effects. Third, untargeted metabolomics analysis revealed that the protective effect was associated with significant changes in metabolism linked to sphingolipid signaling pathways, unsaturated fatty acid biosynthesis, phosphocreatine, glutathione disulfide, aminoacyl-tRNA biosynthesis, and ABC transporters. Conclusions. Our study demonstrated a protective effect of enhanced proline metabolism in cardiomyocytes under hypoxia, providing a novel strategy for exploring new treatments for coronary heart disease.

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“…ABC transporters are a family of ATPdependent transporters that can transport a variety of endogenous compounds, including amino acids, ions, nucleotides, lipids, peptides, and so on, across the cell membrane. Researchers have found that ABC transporters are altered after MI and are involved in cardiac homeostasis [31], [32], which constitute future research directions regarding the cardioprotective effect of proline metabolism.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics analysis of the ameliorative effect of enhanced proline metabolism on hypoxia-induced injury in cardiomyocytes

Wang

Xue

Hua

et al. 2020

Preprint

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Background Coronary heart disease is currently the leading cause of death in humans. Its poor prognosis and high mortality are associated with myocardial ischemia, which leads to metabolic disorder-related cardiomyocyte apoptosis and reactive oxygen species (ROS) production. Previous cardiovascular metabolomics studies in humans and mice have shown that proline metabolism is severely altered after cardiomyocyte hypoxia. Proline dehydrogenase (PRODH) is an enzyme that catalyzes the first step of proline catabolism, which plays an important role in improving the cellular redox state. In vitro oxygen-glucose deprivation can mimic in vivo myocardial ischemic injury. This study aimed to investigate whether enhancing proline metabolism by overexpressing PRODH can ameliorate hypoxia-induced injury in cardiomyocytes and to reveal the related altered metabolites and mechanistic pathway via untargeted metabolomics analysis. Results First, through public database analysis and RT-qPCR and western blot analyses in a cardiomyocyte hypoxia model, we found that the expression of the proline-degrading enzyme PRODH was downregulated after myocardial infarction and hypoxia exposure. Second, LDH assays, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), DHE staining, flow cytometric apoptosis analysis with DCFH and Annexin V-FITC/PI, and western blot analysis were used to assess the injury level in cardiomyocytes. Enhanced proline metabolism induced by PRODH overexpression reduced the levels of reactive oxidative stress and apoptosis, whereas PRODH knockdown had the opposite effects. Third, untargeted metabolomics analysis revealed that the protective effect was associated with significant changes in metabolism linked to sphingolipid signaling pathways, unsaturated fatty acid biosynthesis, phosphocreatine, glutathione disulfide, aminoacyl-tRNA biosynthesis, and ABC transporters. Conclusions Our study demonstrated a protective effect of enhanced proline metabolism in cardiomyocytes under hypoxia, providing a novel strategy for exploring new treatments for coronary heart disease.

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Overview of the Components of Cardiac Metabolism

Cited by 25 publications

References 220 publications

Proteomic and metabolomic characterization of cardiac tissue in acute myocardial ischemia injury rats

Proteomic and metabolomic characterization of cardiac tissue in acute myocardial ischemia injury rats

Metabolomic Analysis of the Ameliorative Effect of Enhanced Proline Metabolism on Hypoxia-Induced Injury in Cardiomyocytes

Metabolomics analysis of the ameliorative effect of enhanced proline metabolism on hypoxia-induced injury in cardiomyocytes

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