Abstract 16817: Overexpression of CARP Exaggerates Cardiac Hypertrophy and Heart Failure by Accumulation of Calcineurin and p53 in Pressure-Overloaded Mice

Background:It is known that the muscle ankyrin repeat protein family member Ankrd1/CARP is markedly augmented in cardiac hypertrophy and heart failure (HF). But, its role and the underlying mechanisms the pathogenesis of cardiac hypertrophy and HF remain unclear. Recently CARP was identified as a co-activator of p53, while p53 was demonstrated to play an important role in the progression of HF. We therefore hypothesized that CARP would accelerate HF by activation of p53. Methods and Results: In transverse aortic constriction (TAC) mouse models, cardiac-restricted overexpression of adenoviral CARP (Ad-CARP, myocardial injection) markedly increased heart to body weight ratio (5.81±0.20 mg/g in TAC-Ad-EGFP group, 8.88±1.54 mg/g in Ad-CARP group, P<0.01) and accelerated cardiac dysfunction (left ventricular fractional shortening:35.69%±4.33% in Ad-EGFP group,26.21%±4.16% in Ad-CARP group, P<0.01; lung to body weight ratio: 6.69±1.10mg/g in TAC-Ad-EGFP group, 12.17±3.21 mg/g in Ad-CARP group, P<0.05). In Ad-CA...