Changes in cardiac substrate transporters and metabolic proteins mirror the metabolic shift in patients with aortic stenosis

Lisa C. Heather*, Neil J. Howell, Yaso Emmanuel, Mark A. Cole, Michael Frenneaux, Domenico Pagano, Kieran Clarke

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

In the hypertrophied human heart, fatty acid metabolism is decreased and glucose utilisation is increased. We hypothesized that the sarcolemmal and mitochondrial proteins involved in these key metabolic pathways would mirror these changes, providing a mechanism to account for the modified metabolic flux measured in the human heart. Echocardiography was performed to assess in vivo hypertrophy and aortic valve impairment in patients with aortic stenosis (n = 18). Cardiac biopsies were obtained during valve replacement surgery, and used for western blotting to measure metabolic protein levels. Protein levels of the predominant fatty acid transporter, fatty acid translocase (FAT/CD36) correlated negatively with levels of the glucose transporters, GLUT1 and GLUT4. The decrease in FAT/CD36 was accompanied by decreases in the fatty acid binding proteins, FABPpm and H-FABP, the beta-oxidation protein medium chain acyl-coenzyme A dehydrogenase, the Krebs cycle protein alpha-ketoglutarate dehydrogenase and the oxidative phosphorylation protein ATP synthase. FAT/CD36 and complex I of the electron transport chain were downregulated, whereas the glucose transporter GLUT4 was upregulated with increasing left ventricular mass index, a measure of cardiac hypertrophy. In conclusion, coordinated downregulation of sequential steps involved in fatty acid and oxidative metabolism occur in the human heart, accompanied by upregulation of the glucose transporters. The profile of the substrate transporters and metabolic proteins mirror the metabolic shift from fatty acid to glucose utilisation that occurs in vivo in the human heart.

Original languageEnglish
Article number26326
Number of pages6
JournalPloS ONE
Volume6
Issue number10
DOIs
Publication statusPublished - 18 Oct 2011

Keywords

  • fatty-acid transport
  • failing human heart
  • idiopathic dilated cardiomyopathy
  • gene-expression
  • rat-heart
  • CD36 deficiency
  • skeletal-muscle
  • binding-protein
  • fat/CD36
  • myocytes

Cite this

Heather, L. C., Howell, N. J., Emmanuel, Y., Cole, M. A., Frenneaux, M., Pagano, D., & Clarke, K. (2011). Changes in cardiac substrate transporters and metabolic proteins mirror the metabolic shift in patients with aortic stenosis. PloS ONE, 6(10), [26326]. https://doi.org/10.1371/journal.pone.0026326