H022 FKBP12.6 overexpression in mouse cardiac myocytes offers minor protection against pressure overload-induced cardiac remodelling and failure - 17/04/09
Résumé |
Alterations in RyR2 function is a hallmark of heart failure (HF). Decreased FKBP12.6 binding to RyR2 has been put forward to explain the diastolic SR Ca2+ leakage observed in this condition. Previous work in the mouse has shown that cardiac FKBP12.6 overexpression protects against the development of myocardial infarction-induced heart failure. Using a mouse model of conditional cardiac-specific FKBP12.6 overexpression, we tested the hypothesis that this overexpression protects against transverse aortic constriction (TAC)-induced cardiac remodelling and failure.
Ten weeks after TAC, male transgenic (DT) and their littermates controls (Ctr) underwent heart catheterization. Ventricular expression of the hypertrophic gene program and calcium handling proteins were assessed by real-time PCR and Western blot, respectively.Ten weeks after TAC, the mortality rate was 23 % in Ctr and 13 % in DT (14/60 vs 5/39, ns). The percentage of mice with HF, based on pulmonary oedema, was 42 % in Ctr-TAC and 32 % in DT-TAC (15/36 vs 7/22, ns). Gravimetric and hemodynamic data are shown in the table:
|
BNP mRNA level increased 2.8 fold in Ctr-TAC (P<0.01 vs Ctr-Sham) and 2.4 fold in DT-TAC (P<0.01 vs DT-Sham).⍺-skeletal actin mRNA level increased 4.3 fold in Ctr-TAC (P<0.001 vs Ctr-Sham) and 3.8 fold in DT-TAC (P<0.001 vs DT-Sham). β-MHC/⍺-MHC mRNA ratio increased 2.8 fold in Ctr-TAC (P<0.01 vs Ctr-Sham) and 4.3 fold in DT-TAC (P<0.05 vs DT-Sham). RyR2 protein level decreased by 58 % in Ctr-TAC and 41 % in DT-TAC (P<0.01 and P<0.05 vs respective Sham). SERCA2a protein level decreased by 29 % in Ctr-TAC and 16 % in DT-TAC (P<0.01 and P<0.05 vs respective Sham). No statistical difference was found between DT-TAC and Ctr-TAC for any of these parameters.
Conclusion |
Cardiac FKBP 12.6 overexpression offers weak protection if any against TAC-induced cardiac remodeling and failure in the mouse.
Le texte complet de cet article est disponible en PDF.Plan
Vol 102 - N° S1
P. S79-S80 - mars 2009 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.