Format

Send to

Choose Destination
Biochem Biophys Res Commun. 2006 Feb 10;340(2):702-8. Epub 2005 Dec 20.

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

Author information

1
University of Technology Dresden, Department of Cardiology, Medical Clinic, Fetscherstr. 76, D-01307 Dresden, Germany. carstenwunderlich@gmx.de

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.

PMID:
16380094
DOI:
10.1016/j.bbrc.2005.12.058
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center