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

Carsten Wunderlich; Kristin Schober; Stefan A Lange; Marek Drab; Ruediger C Braun-Dullaeus; Michael Kasper; Carsten Schwencke; Alexander Schmeisser; Ruth H Strasser

doi:10.1016/j.bbrc.2005.12.058

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

Biochem Biophys Res Commun. 2006 Feb 10;340(2):702-8. doi: 10.1016/j.bbrc.2005.12.058. Epub 2005 Dec 20.

Authors

Carsten Wunderlich¹, Kristin Schober, Stefan A Lange, Marek Drab, Ruediger C Braun-Dullaeus, Michael Kasper, Carsten Schwencke, Alexander Schmeisser, Ruth H Strasser

Affiliation

¹ University of Technology Dresden, Department of Cardiology, Medical Clinic, Fetscherstr. 76, D-01307 Dresden, Germany. [email protected]

PMID: 16380094
DOI: 10.1016/j.bbrc.2005.12.058

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.

MeSH terms

Adenosine Triphosphate / metabolism
Animals
Apoptosis / genetics
Cardiomyopathy, Hypertrophic / enzymology
Cardiomyopathy, Hypertrophic / genetics
Cardiomyopathy, Hypertrophic / metabolism*
Cardiomyopathy, Hypertrophic / physiopathology
Caveolin 1 / deficiency*
Caveolin 1 / genetics*
Cyclic AMP / metabolism
Heart Failure / genetics
Heart Failure / metabolism*
Heart Failure / physiopathology
Hypertrophy, Left Ventricular / enzymology
Hypertrophy, Left Ventricular / genetics
Hypertrophy, Left Ventricular / physiopathology
Hypertrophy, Right Ventricular / enzymology
Hypertrophy, Right Ventricular / genetics
Hypertrophy, Right Ventricular / physiopathology
Mice
Mice, Knockout
Mice, Transgenic
Myocardium / enzymology
Myocardium / metabolism*
Nitric Oxide / metabolism*
Nitric Oxide Synthase Type II / metabolism
Nitric Oxide Synthase Type III / metabolism*
Severity of Illness Index

Substances

Caveolin 1
Nitric Oxide
Adenosine Triphosphate
Cyclic AMP
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Nos3 protein, mouse