Substrate uptake and metabolism are preserved in hypertrophic caveolin-3 knockout hearts

Ayanna S. Augustus, Jonathan Buchanan, Sankar Addya, Giuseppe Rengo, Richard G. Pestell, Paolo Fortina, Walter J. Koch, Andre Bensadoun, E. Dale Abel, Michael P. Lisanti

Research output: Contribution to journalArticlepeer-review


Caveolin-3 (Cav3), the primary protein component of caveolae in muscle cells, regulates numerous signaling pathways including insulin receptor signaling and facilitates free fatty acid (FA) uptake by interacting with several FA transport proteins. We previously reported that Cav3 knockout mice (Cav3KO) develop cardiac hypertrophy with diminished contractile function; however, the effects of Cav3 gene ablation on cardiac substrate utilization are unknown. The present study revealed that the uptake and oxidation of FAs and glucose were normal in hypertrophic Cav3KO hearts. Real-time PCR analysis revealed normal expression of lipid metabolism genes including FA translocase (CD36) and carnitine palmitoyl transferase-1 in Cav3KO hearts. Interestingly, myocardial cAMP content was significantly increased by 42%; however, this had no effect on PKA activity in Cav3KO hearts. Microarray expression analysis revealed a marked increase in the expression of genes involved in receptor trafficking to the plasma membrane, including Rab4a and the expression of WD repeat/FYVE domain containing proteins. We observed a fourfold increase in the expression of cellular retinol binding protein-III and a 3.5-fold increase in 17β-hydroxysteroid dehydrogenase type 11, a member of the short-chain dehydrogenase/reductase family involved in the biosynthesis and inactivation of steroid hormones. In summary, a loss of Cav3 in the heart leads to cardiac hypertrophy with normal substrate utilization. Moreover, a loss of Cav3 mRNA altered the expression of several genes not previously linked to cardiac growth and function. Thus we have identified a number of new target genes associated with the pathogenesis of cardiac hypertrophy.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number2
Publication statusPublished - Aug 2008


  • Adenosine 3′,5′-cyclic monophosphate
  • Cardiomyopathy
  • Caveolae
  • Fatty acids
  • Isolated perfused hearts

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Substrate uptake and metabolism are preserved in hypertrophic caveolin-3 knockout hearts'. Together they form a unique fingerprint.

Cite this