Analysis of metabolic remodeling in compensated left ventricular hypertrophy and heart failure

Takao Kato, Shinichiro Niizuma, Yasutaka Inuzuka, Tsuneaki Kawashima, Junji Okuda, Yodo Tamaki, Yoshitaka Iwanaga, Michiko Narazaki, Tetsuya Matsuda, Tomoyoshi Soga, Toru Kita, Takeshi Kimura, Tetsuo Shioi

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Background: Congestive heart failure (CHF) is associated with a change in cardiac energy metabolism. However, the mechanism by which this change is induced and causes the progression of CHF is unclear. Methods and Results: We analyzed the cardiac energy metabolism of Dahl salt-sensitive rats fed a high-salt diet, which showed a distinct transition from compensated left ventricular hypertrophy to CHF. Glucose uptake increased at the left ventricular hypertrophy stage, and glucose uptake further increased and fatty acid uptake decreased at the CHF stage. The gene expression related to glycolysis, fatty acid oxidation, and mitochondrial function was preserved at the left ventricular hypertrophy stage but decreased at the CHF stage and was associated with decreases in levels of transcriptional regulators. In a comprehensive metabolome analysis, the pentose phosphate pathway that regulates the cellular redox state was found to be activated at the CHF stage. Dichloroacetate (DCA), a compound known to enhance glucose oxidation, increased energy reserves and glucose uptake. DCA improved cardiac function and the survival of the animals. DCA activated the pentose phosphate pathway in the rat heart. DCA activated the pentose phosphate pathway, decreased oxidative stress, and prevented cell death of cultured cardiomyocytes. Conclusions: Left ventricular hypertrophy or CHF is associated with a distinct change in the metabolic profile of the heart. DCA attenuated the transition associated with increased energy reserves, activation of the pentose phosphate pathway, and reduced oxidative stress.

Original languageEnglish
Pages (from-to)420-430
Number of pages11
JournalCirculation: Heart Failure
Volume3
Issue number3
DOIs
Publication statusPublished - 2010 May

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Left Ventricular Hypertrophy
Heart Failure
Pentose Phosphate Pathway
Glucose
Metabolome
Energy Metabolism
Oxidative Stress
Fatty Acids
Inbred Dahl Rats
Glycolysis
Cardiac Myocytes
Oxidation-Reduction
Cell Death
Salts
Diet
Gene Expression

Keywords

  • Dichloroacetate
  • Glycolysis
  • Heart failure
  • Hypertrophy
  • Pentose phosphate pathway

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Kato, T., Niizuma, S., Inuzuka, Y., Kawashima, T., Okuda, J., Tamaki, Y., ... Shioi, T. (2010). Analysis of metabolic remodeling in compensated left ventricular hypertrophy and heart failure. Circulation: Heart Failure, 3(3), 420-430. https://doi.org/10.1161/CIRCHEARTFAILURE.109.888479

Analysis of metabolic remodeling in compensated left ventricular hypertrophy and heart failure. / Kato, Takao; Niizuma, Shinichiro; Inuzuka, Yasutaka; Kawashima, Tsuneaki; Okuda, Junji; Tamaki, Yodo; Iwanaga, Yoshitaka; Narazaki, Michiko; Matsuda, Tetsuya; Soga, Tomoyoshi; Kita, Toru; Kimura, Takeshi; Shioi, Tetsuo.

In: Circulation: Heart Failure, Vol. 3, No. 3, 05.2010, p. 420-430.

Research output: Contribution to journalArticle

Kato, T, Niizuma, S, Inuzuka, Y, Kawashima, T, Okuda, J, Tamaki, Y, Iwanaga, Y, Narazaki, M, Matsuda, T, Soga, T, Kita, T, Kimura, T & Shioi, T 2010, 'Analysis of metabolic remodeling in compensated left ventricular hypertrophy and heart failure', Circulation: Heart Failure, vol. 3, no. 3, pp. 420-430. https://doi.org/10.1161/CIRCHEARTFAILURE.109.888479
Kato, Takao ; Niizuma, Shinichiro ; Inuzuka, Yasutaka ; Kawashima, Tsuneaki ; Okuda, Junji ; Tamaki, Yodo ; Iwanaga, Yoshitaka ; Narazaki, Michiko ; Matsuda, Tetsuya ; Soga, Tomoyoshi ; Kita, Toru ; Kimura, Takeshi ; Shioi, Tetsuo. / Analysis of metabolic remodeling in compensated left ventricular hypertrophy and heart failure. In: Circulation: Heart Failure. 2010 ; Vol. 3, No. 3. pp. 420-430.
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