Disruption of caveolin-1 leads to enhanced nitrosative stress and severe systolic and diastolic heart failure

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Carsten Wunderlich - , Medical clinic with a focus on cardiology (at the Heart Center) (Author)
  • Kristin Schober - , Medical clinic with a focus on cardiology (at the Heart Center) (Author)
  • Stefan A. Lange - , Medical clinic with a focus on cardiology (at the Heart Center) (Author)
  • Marek Drab - , Institute of Pharmacology and Toxicology (Author)
  • Ruediger C. Braun-Dullaeus - , Medical clinic with a focus on cardiology (at the Heart Center) (Author)
  • Michael Kasper - , Institute of Anatomy (Author)
  • Carsten Schwencke - , Medical clinic with a focus on cardiology (at the Heart Center) (Author)
  • Alexander Schmeisser - , Medical clinic with a focus on cardiology (at the Heart Center) (Author)
  • Ruth H. Strasser - , Medical clinic with a focus on cardiology (at the Heart Center) (Author)

Abstract

Although caveolin-1 is not expressed in cardiomyocytes, this protein is assumed to act as a key regulator in the development of cardiomyopathy. In view of recent discordant findings we aimed to elucidate the cardiac phenotype of independently generated caveolin-1 knockout mice (cav-1-/-) and to unveil causative mechanisms. Invasive hemodynamic measurements of cav-1 -/- show a severely reduced systolic and diastolic heart function. Additionally, genetic ablation of caveolin-1 leads to a striking biventricular hypertrophy and to a sustained eNOS-hyperactivation yielding increased systemic NO levels. Furthermore, a diminished ATP content and reduced levels of cyclic AMP in hearts of knockout animals were measured. Taken together, these results indicate that genetic disruption of caveolin-1 is sufficient to induce a severe biventricular hypertrophy with signs of systolic and diastolic heart failure. Collectively, our findings suggest a causative role of a sustained nitrosative stress in the development of the pronounced cardiac impairment.

Details

Original languageEnglish
Pages (from-to)702-708
Number of pages7
JournalBiochemical and biophysical research communications
Volume340
Issue number2
Publication statusPublished - 10 Feb 2006
Peer-reviewedYes

External IDs

PubMed 16380094

Keywords

Keywords

  • Cardiac contractility and hemodynamics, Caveolin, eNOS, Nitric oxide