GLUT1 deficiency in cardiomyocytes does not accelerate the transition from compensated hypertrophy to heart failure

Renata O. Pereira, Adam R. Wende, Curtis Olsen, Jamie Soto, Tenley Rawlings, Yi Zhu, Christian Riehle, E. Dale Abel

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The aim of this study was to determine whether endogenous GLUT1 induction and the increased glucose utilization that accompanies pressure overload hypertrophy (POH) are required to maintain cardiac function during hemodynamic stress, and to test the hypothesis that lack of GLUT1 will accelerate the transition to heart failure. To determine the contribution of endogenous GLUT1 to the cardiac adaptation to POH, male mice with cardiomyocyte-restricted deletion of the GLUT1 gene (G1KO) and their littermate controls (Cont) were subjected to transverse aortic constriction (TAC). GLUT1 deficiency reduced glycolysis and glucose oxidation by 50%, which was associated with a reciprocal increase in fatty acid oxidation (FAO) relative to controls. Four weeks after TAC, glycolysis increased and FAO decreased by 50% in controls, but were unchanged in G1KO hearts relative to shams. G1KO and controls exhibited equivalent degrees of cardiac hypertrophy, fibrosis, and capillary density loss after TAC. Following TAC, in vivo left ventricular developed pressure was decreased in G1KO hearts relative to controls, but. +. dP/dt was equivalently reduced in Cont and G1KO mice. Mitochondrial function was equivalently impaired following TAC in both Cont and G1KO hearts. GLUT1 deficiency in cardiomyocytes alters myocardial substrate utilization, but does not substantially exacerbate pressure-overload induced contractile dysfunction or accelerate the progression to heart failure.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume72
DOIs
StatePublished - Jan 1 2014

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Cardiac Myocytes
Constriction
Hypertrophy
Heart Failure
Glycolysis
Pressure
Fatty Acids
Glucose
Gene Deletion
Cardiomegaly
Ventricular Pressure
Exercise Test
Fibrosis
Hemodynamics

Keywords

  • Cardiac hypertrophy
  • Cardiac metabolism
  • Glucose transport

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

GLUT1 deficiency in cardiomyocytes does not accelerate the transition from compensated hypertrophy to heart failure. / Pereira, Renata O.; Wende, Adam R.; Olsen, Curtis; Soto, Jamie; Rawlings, Tenley; Zhu, Yi; Riehle, Christian; Abel, E. Dale.

In: Journal of Molecular and Cellular Cardiology, Vol. 72, 01.01.2014, p. 95-103.

Research output: Contribution to journalArticle

Pereira, Renata O. ; Wende, Adam R. ; Olsen, Curtis ; Soto, Jamie ; Rawlings, Tenley ; Zhu, Yi ; Riehle, Christian ; Abel, E. Dale. / GLUT1 deficiency in cardiomyocytes does not accelerate the transition from compensated hypertrophy to heart failure. In: Journal of Molecular and Cellular Cardiology. 2014 ; Vol. 72. pp. 95-103.
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