Clin Res Cardiol 100, Suppl 1, April 2011

P649 - Caveolin-1/eNOS double knockout mice display significant proteomic changes which possibly account for their normalized cardiac phenotype
A. Brandt1, F. Heidenreich2, N. Steinbronn1, J. Lehmann1, S. Lenhard3, C. Czupalla3, B. Hoflack3, R. Marquetant1, T. Kriegel2, R. H. Strasser1, C. Wunderlich1
1Klinik für Innere Medizin, Kardiologie und Intensivmedizin, TU Universität Dresden, Herzzentrum Dresden Universitätsklinik, Dresden; 2Institut für Physiologische Chemie, Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Dresden; 3Department of Proteomics, Biotechnologisches Zentrum, Technische Universität Dresden, Dresden;
Caveolin-1 knockout mice (cav1-ko) display a severely diseased cardiac phenotype with a marked hypertrophic cardiomyopathy and signs of advanced heart failure. Recent pharmacological studies suggest a crucial role of a hyperactivated endothelial nitric oxide synthase (eNOS) with partial eNOS-uncoupling in this model. This provided the rationale to study the role of eNOS in this context, using a genetic approach, i.e. examining eNOS knockout mice (eNOS-ko) as well as newly generated Caveolin-1/eNOS double knockout mice (cav1/eNOS-ko).
Echocardiographic and hemodynamic measurements could detect a normalized cardiac phenotype in cav1/eNOS-ko. Additionally, these improvements translate into an improved physical ability of the double knockout mice in swimming tests. To screen for further molecular differences a proteomic approach was chosen in the present study: Protein samples from whole hearts of wildtype, eNOS-ko, cav1-ko and cav1/eNOS-ko (n=3) were subjected to two dimensional difference gel electrophoresis (2D-DIGE) with subsequent identification of proteomic differences via matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF). Thirteen spots that showed significantly altered intensities (p<0.05, ANOVA) were analyzed. This yielded ten positive identifications of eight different proteins which were altered between the strains. Interestingly, these newly identified proteins have an established role in energy metabolism (i.e. short-chain specific acyl-CoA dehydrogenase, ACADS), and oxidative stress response (i.e. Peroxiredoxin-6, PRDX6).
Employing a proteomic approach the present study identified significant molecular changes in cav1/eNOS-ko which might contribute to the cardiac recovery of these animals. Especially the reversal of cardiac hypertrophy indicates that growth and potentially proliferation may be involved in these processes. Whether these molecular changes are involved in the development of other forms of cardiomyopathy is focus of further ongoing studies.
Clin Res Cardiol 100, Suppl 1, April 2011
Zitierung mit Vortrags- oder Posternummer s.o.
DOI 10.1007/s00392-011-1100-y