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Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure
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| Zeitschriftentitel: | Circulation: Cardiovascular Genetics |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , |
| In: | Circulation: Cardiovascular Genetics, 7, 2014, 3, S. 266-276 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Ovid Technologies (Wolters Kluwer Health)
|
| Schlagwörter: |
| author_facet |
Gupte, Anisha A. Hamilton, Dale J. Cordero-Reyes, Andrea M. Youker, Keith A. Yin, Zheng Estep, Jerry D. Stevens, Robert D. Wenner, Brett Ilkayeva, Olga Loebe, Matthias Peterson, Leif E. Lyon, Christopher J. Wong, Stephen T.C. Newgard, Christopher B. Torre-Amione, Guillermo Taegtmeyer, Heinrich Hsueh, Willa A. Gupte, Anisha A. Hamilton, Dale J. Cordero-Reyes, Andrea M. Youker, Keith A. Yin, Zheng Estep, Jerry D. Stevens, Robert D. Wenner, Brett Ilkayeva, Olga Loebe, Matthias Peterson, Leif E. Lyon, Christopher J. Wong, Stephen T.C. Newgard, Christopher B. Torre-Amione, Guillermo Taegtmeyer, Heinrich Hsueh, Willa A. |
|---|---|
| author |
Gupte, Anisha A. Hamilton, Dale J. Cordero-Reyes, Andrea M. Youker, Keith A. Yin, Zheng Estep, Jerry D. Stevens, Robert D. Wenner, Brett Ilkayeva, Olga Loebe, Matthias Peterson, Leif E. Lyon, Christopher J. Wong, Stephen T.C. Newgard, Christopher B. Torre-Amione, Guillermo Taegtmeyer, Heinrich Hsueh, Willa A. |
| spellingShingle |
Gupte, Anisha A. Hamilton, Dale J. Cordero-Reyes, Andrea M. Youker, Keith A. Yin, Zheng Estep, Jerry D. Stevens, Robert D. Wenner, Brett Ilkayeva, Olga Loebe, Matthias Peterson, Leif E. Lyon, Christopher J. Wong, Stephen T.C. Newgard, Christopher B. Torre-Amione, Guillermo Taegtmeyer, Heinrich Hsueh, Willa A. Circulation: Cardiovascular Genetics Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure Genetics (clinical) Cardiology and Cardiovascular Medicine Genetics |
| author_sort |
gupte, anisha a. |
| spelling |
Gupte, Anisha A. Hamilton, Dale J. Cordero-Reyes, Andrea M. Youker, Keith A. Yin, Zheng Estep, Jerry D. Stevens, Robert D. Wenner, Brett Ilkayeva, Olga Loebe, Matthias Peterson, Leif E. Lyon, Christopher J. Wong, Stephen T.C. Newgard, Christopher B. Torre-Amione, Guillermo Taegtmeyer, Heinrich Hsueh, Willa A. 1942-325X 1942-3268 Ovid Technologies (Wolters Kluwer Health) Genetics (clinical) Cardiology and Cardiovascular Medicine Genetics http://dx.doi.org/10.1161/circgenetics.113.000404 <jats:sec> <jats:title>Background—</jats:title> <jats:p>Impaired bioenergetics is a prominent feature of the failing heart, but the underlying metabolic perturbations are poorly understood.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> We compared metabolomic, gene transcript, and protein data from 6 paired samples of failing human left ventricular tissue obtained during left ventricular assist device insertion (heart failure samples) and at heart transplant (post-left ventricular assist device samples). Nonfailing left ventricular wall samples procured from explanted hearts of patients with right heart failure served as novel comparison samples. Metabolomic analyses uncovered a distinct pattern in heart failure tissue: 2.6-fold increased pyruvate concentrations coupled with reduced Krebs cycle intermediates and short-chain acylcarnitines, suggesting a global reduction in substrate oxidation. These findings were associated with decreased transcript levels for enzymes that catalyze fatty acid oxidation and pyruvate metabolism and for key transcriptional regulators of mitochondrial metabolism and biogenesis, peroxisome proliferator-activated receptor γ coactivator 1α ( <jats:italic>PGC1A</jats:italic> , 1.3-fold) and estrogen-related receptor α ( <jats:italic>ERRA</jats:italic> , 1.2-fold) and γ ( <jats:italic>ERRG</jats:italic> , 2.2-fold). Thus, parallel decreases in key transcription factors and their target metabolic enzyme genes can explain the decreases in associated metabolic intermediates. Mechanical support with left ventricular assist device improved all of these metabolic and transcriptional defects. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>These observations underscore an important pathophysiologic role for severely defective metabolism in heart failure, while the reversibility of these defects by left ventricular assist device suggests metabolic resilience of the human heart.</jats:p> </jats:sec> Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure Circulation: Cardiovascular Genetics |
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10.1161/circgenetics.113.000404 |
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Circulation: Cardiovascular Genetics |
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| title |
Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure |
| title_unstemmed |
Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure |
| title_full |
Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure |
| title_fullStr |
Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure |
| title_full_unstemmed |
Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure |
| title_short |
Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure |
| title_sort |
mechanical unloading promotes myocardial energy recovery in human heart failure |
| topic |
Genetics (clinical) Cardiology and Cardiovascular Medicine Genetics |
| url |
http://dx.doi.org/10.1161/circgenetics.113.000404 |
| publishDate |
2014 |
| physical |
266-276 |
| description |
<jats:sec>
<jats:title>Background—</jats:title>
<jats:p>Impaired bioenergetics is a prominent feature of the failing heart, but the underlying metabolic perturbations are poorly understood.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods and Results—</jats:title>
<jats:p>
We compared metabolomic, gene transcript, and protein data from 6 paired samples of failing human left ventricular tissue obtained during left ventricular assist device insertion (heart failure samples) and at heart transplant (post-left ventricular assist device samples). Nonfailing left ventricular wall samples procured from explanted hearts of patients with right heart failure served as novel comparison samples. Metabolomic analyses uncovered a distinct pattern in heart failure tissue: 2.6-fold increased pyruvate concentrations coupled with reduced Krebs cycle intermediates and short-chain acylcarnitines, suggesting a global reduction in substrate oxidation. These findings were associated with decreased transcript levels for enzymes that catalyze fatty acid oxidation and pyruvate metabolism and for key transcriptional regulators of mitochondrial metabolism and biogenesis, peroxisome proliferator-activated receptor γ coactivator 1α (
<jats:italic>PGC1A</jats:italic>
, 1.3-fold) and estrogen-related receptor α (
<jats:italic>ERRA</jats:italic>
, 1.2-fold) and γ (
<jats:italic>ERRG</jats:italic>
, 2.2-fold). Thus, parallel decreases in key transcription factors and their target metabolic enzyme genes can explain the decreases in associated metabolic intermediates. Mechanical support with left ventricular assist device improved all of these metabolic and transcriptional defects.
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions—</jats:title>
<jats:p>These observations underscore an important pathophysiologic role for severely defective metabolism in heart failure, while the reversibility of these defects by left ventricular assist device suggests metabolic resilience of the human heart.</jats:p>
</jats:sec> |
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| author | Gupte, Anisha A., Hamilton, Dale J., Cordero-Reyes, Andrea M., Youker, Keith A., Yin, Zheng, Estep, Jerry D., Stevens, Robert D., Wenner, Brett, Ilkayeva, Olga, Loebe, Matthias, Peterson, Leif E., Lyon, Christopher J., Wong, Stephen T.C., Newgard, Christopher B., Torre-Amione, Guillermo, Taegtmeyer, Heinrich, Hsueh, Willa A. |
| author_facet | Gupte, Anisha A., Hamilton, Dale J., Cordero-Reyes, Andrea M., Youker, Keith A., Yin, Zheng, Estep, Jerry D., Stevens, Robert D., Wenner, Brett, Ilkayeva, Olga, Loebe, Matthias, Peterson, Leif E., Lyon, Christopher J., Wong, Stephen T.C., Newgard, Christopher B., Torre-Amione, Guillermo, Taegtmeyer, Heinrich, Hsueh, Willa A., Gupte, Anisha A., Hamilton, Dale J., Cordero-Reyes, Andrea M., Youker, Keith A., Yin, Zheng, Estep, Jerry D., Stevens, Robert D., Wenner, Brett, Ilkayeva, Olga, Loebe, Matthias, Peterson, Leif E., Lyon, Christopher J., Wong, Stephen T.C., Newgard, Christopher B., Torre-Amione, Guillermo, Taegtmeyer, Heinrich, Hsueh, Willa A. |
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| description | <jats:sec> <jats:title>Background—</jats:title> <jats:p>Impaired bioenergetics is a prominent feature of the failing heart, but the underlying metabolic perturbations are poorly understood.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> We compared metabolomic, gene transcript, and protein data from 6 paired samples of failing human left ventricular tissue obtained during left ventricular assist device insertion (heart failure samples) and at heart transplant (post-left ventricular assist device samples). Nonfailing left ventricular wall samples procured from explanted hearts of patients with right heart failure served as novel comparison samples. Metabolomic analyses uncovered a distinct pattern in heart failure tissue: 2.6-fold increased pyruvate concentrations coupled with reduced Krebs cycle intermediates and short-chain acylcarnitines, suggesting a global reduction in substrate oxidation. These findings were associated with decreased transcript levels for enzymes that catalyze fatty acid oxidation and pyruvate metabolism and for key transcriptional regulators of mitochondrial metabolism and biogenesis, peroxisome proliferator-activated receptor γ coactivator 1α ( <jats:italic>PGC1A</jats:italic> , 1.3-fold) and estrogen-related receptor α ( <jats:italic>ERRA</jats:italic> , 1.2-fold) and γ ( <jats:italic>ERRG</jats:italic> , 2.2-fold). Thus, parallel decreases in key transcription factors and their target metabolic enzyme genes can explain the decreases in associated metabolic intermediates. Mechanical support with left ventricular assist device improved all of these metabolic and transcriptional defects. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>These observations underscore an important pathophysiologic role for severely defective metabolism in heart failure, while the reversibility of these defects by left ventricular assist device suggests metabolic resilience of the human heart.</jats:p> </jats:sec> |
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| spelling | Gupte, Anisha A. Hamilton, Dale J. Cordero-Reyes, Andrea M. Youker, Keith A. Yin, Zheng Estep, Jerry D. Stevens, Robert D. Wenner, Brett Ilkayeva, Olga Loebe, Matthias Peterson, Leif E. Lyon, Christopher J. Wong, Stephen T.C. Newgard, Christopher B. Torre-Amione, Guillermo Taegtmeyer, Heinrich Hsueh, Willa A. 1942-325X 1942-3268 Ovid Technologies (Wolters Kluwer Health) Genetics (clinical) Cardiology and Cardiovascular Medicine Genetics http://dx.doi.org/10.1161/circgenetics.113.000404 <jats:sec> <jats:title>Background—</jats:title> <jats:p>Impaired bioenergetics is a prominent feature of the failing heart, but the underlying metabolic perturbations are poorly understood.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods and Results—</jats:title> <jats:p> We compared metabolomic, gene transcript, and protein data from 6 paired samples of failing human left ventricular tissue obtained during left ventricular assist device insertion (heart failure samples) and at heart transplant (post-left ventricular assist device samples). Nonfailing left ventricular wall samples procured from explanted hearts of patients with right heart failure served as novel comparison samples. Metabolomic analyses uncovered a distinct pattern in heart failure tissue: 2.6-fold increased pyruvate concentrations coupled with reduced Krebs cycle intermediates and short-chain acylcarnitines, suggesting a global reduction in substrate oxidation. These findings were associated with decreased transcript levels for enzymes that catalyze fatty acid oxidation and pyruvate metabolism and for key transcriptional regulators of mitochondrial metabolism and biogenesis, peroxisome proliferator-activated receptor γ coactivator 1α ( <jats:italic>PGC1A</jats:italic> , 1.3-fold) and estrogen-related receptor α ( <jats:italic>ERRA</jats:italic> , 1.2-fold) and γ ( <jats:italic>ERRG</jats:italic> , 2.2-fold). Thus, parallel decreases in key transcription factors and their target metabolic enzyme genes can explain the decreases in associated metabolic intermediates. Mechanical support with left ventricular assist device improved all of these metabolic and transcriptional defects. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>These observations underscore an important pathophysiologic role for severely defective metabolism in heart failure, while the reversibility of these defects by left ventricular assist device suggests metabolic resilience of the human heart.</jats:p> </jats:sec> Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure Circulation: Cardiovascular Genetics |
| spellingShingle | Gupte, Anisha A., Hamilton, Dale J., Cordero-Reyes, Andrea M., Youker, Keith A., Yin, Zheng, Estep, Jerry D., Stevens, Robert D., Wenner, Brett, Ilkayeva, Olga, Loebe, Matthias, Peterson, Leif E., Lyon, Christopher J., Wong, Stephen T.C., Newgard, Christopher B., Torre-Amione, Guillermo, Taegtmeyer, Heinrich, Hsueh, Willa A., Circulation: Cardiovascular Genetics, Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure, Genetics (clinical), Cardiology and Cardiovascular Medicine, Genetics |
| title | Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure |
| title_full | Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure |
| title_fullStr | Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure |
| title_full_unstemmed | Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure |
| title_short | Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure |
| title_sort | mechanical unloading promotes myocardial energy recovery in human heart failure |
| title_unstemmed | Mechanical Unloading Promotes Myocardial Energy Recovery in Human Heart Failure |
| topic | Genetics (clinical), Cardiology and Cardiovascular Medicine, Genetics |
| url | http://dx.doi.org/10.1161/circgenetics.113.000404 |