Skip to main content

Mechanical unloading promotes myocardial energy recovery in human heart failure.

Publication ,  Journal Article
Gupte, AA; Hamilton, DJ; Cordero-Reyes, AM; Youker, KA; Yin, Z; Estep, JD; Stevens, RD; Wenner, B; Ilkayeva, O; Loebe, M; Peterson, LE ...
Published in: Circ Cardiovasc Genet
June 2014

BACKGROUND: Impaired bioenergetics is a prominent feature of the failing heart, but the underlying metabolic perturbations are poorly understood. METHODS AND RESULTS: 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 (PGC1A, 1.3-fold) and estrogen-related receptor α (ERRA, 1.2-fold) and γ (ERRG, 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. CONCLUSIONS: 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.

Duke Scholars

Published In

Circ Cardiovasc Genet

DOI

EISSN

1942-3268

Publication Date

June 2014

Volume

7

Issue

3

Start / End Page

266 / 276

Location

United States

Related Subject Headings

  • Transcription Factors
  • Myocytes, Cardiac
  • Myocardium
  • Middle Aged
  • Male
  • Humans
  • Heart-Assist Devices
  • Heart Ventricles
  • Heart Failure
  • Gene Expression Profiling
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gupte, A. A., Hamilton, D. J., Cordero-Reyes, A. M., Youker, K. A., Yin, Z., Estep, J. D., … Hsueh, W. A. (2014). Mechanical unloading promotes myocardial energy recovery in human heart failure. Circ Cardiovasc Genet, 7(3), 266–276. https://doi.org/10.1161/CIRCGENETICS.113.000404
Gupte, Anisha A., Dale J. Hamilton, Andrea M. Cordero-Reyes, Keith A. Youker, Zheng Yin, Jerry D. Estep, Robert D. Stevens, et al. “Mechanical unloading promotes myocardial energy recovery in human heart failure.Circ Cardiovasc Genet 7, no. 3 (June 2014): 266–76. https://doi.org/10.1161/CIRCGENETICS.113.000404.
Gupte AA, Hamilton DJ, Cordero-Reyes AM, Youker KA, Yin Z, Estep JD, et al. Mechanical unloading promotes myocardial energy recovery in human heart failure. Circ Cardiovasc Genet. 2014 Jun;7(3):266–76.
Gupte, Anisha A., et al. “Mechanical unloading promotes myocardial energy recovery in human heart failure.Circ Cardiovasc Genet, vol. 7, no. 3, June 2014, pp. 266–76. Pubmed, doi:10.1161/CIRCGENETICS.113.000404.
Gupte AA, Hamilton DJ, Cordero-Reyes AM, Youker KA, Yin Z, Estep JD, Stevens RD, Wenner B, Ilkayeva O, Loebe M, Peterson LE, Lyon CJ, Wong STC, Newgard CB, Torre-Amione G, Taegtmeyer H, Hsueh WA. Mechanical unloading promotes myocardial energy recovery in human heart failure. Circ Cardiovasc Genet. 2014 Jun;7(3):266–276.

Published In

Circ Cardiovasc Genet

DOI

EISSN

1942-3268

Publication Date

June 2014

Volume

7

Issue

3

Start / End Page

266 / 276

Location

United States

Related Subject Headings

  • Transcription Factors
  • Myocytes, Cardiac
  • Myocardium
  • Middle Aged
  • Male
  • Humans
  • Heart-Assist Devices
  • Heart Ventricles
  • Heart Failure
  • Gene Expression Profiling