Abstract 3599: Ras-Association Domain Family 1 Isoform A (RASSF1A)Inhibits Myocardial Hypertrophy by Blocking Signal Transmission From Ras to Raf1

Understanding the molecular mechanisms of cardiac hypertrophy is key in elucidating the pathogenesis of heart failure. Many factors that positively mediate hypertrophy have been identified in recent years, but little is known about counteracting negative regulators. The tumour suppressor RASSF1A (Ras-Association Domain Family 1 Isoform A) has recently been described as a regulator of cell proliferation and apoptosis in cancer cells. Although we and others have detected RASSF1A expression in the heart, little is known about its (patho-)physiological functions. Here we investigate the role of this molecule in regulating myocardial hypertrophy in mouse and man. Ablation of RASSF1A in mice (RASSF1A KO) significantly enhanced the hypertrophic response to transverse aortic constriction/TAC (64.7% increase in heart weight/body weight ratio in RASSF1A KO mice compared to 30.6% in wild type (WT), n=10, P