| First Author | Wunderlich C | Year | 2006 |
| Journal | Biochem Biophys Res Commun | Volume | 340 |
| Issue | 2 | Pages | 702-8 |
| PubMed ID | 16380094 | Mgi Jnum | J:104734 |
| Mgi Id | MGI:3612726 | Doi | 10.1016/j.bbrc.2005.12.058 |
| Citation | Wunderlich C, et al. (2006) Disruption of caveolin-1 leads to enhanced nitrosative stress and severe systolic and diastolic heart failure. Biochem Biophys Res Commun 340(2):702-8 |
| abstractText | 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. |
