Disruption of caveolin-1 leads to enhanced nitrosative stress and severe systolic and diastolic heart failure
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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 language | English |
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Pages (from-to) | 702-708 |
Number of pages | 7 |
Journal | Biochemical and biophysical research communications |
Volume | 340 |
Issue number | 2 |
Publication status | Published - 10 Feb 2006 |
Peer-reviewed | Yes |
External IDs
PubMed | 16380094 |
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Keywords
ASJC Scopus subject areas
Keywords
- Cardiac contractility and hemodynamics, Caveolin, eNOS, Nitric oxide