Physiological cardiac hypertrophy associated with regular exercise is usually beneficial, in marked contrast to pathological hypertrophy associated with disease. 14-3-3 proteins play a critical antiapoptotic function in cardiomyocytes. Whether it or other genes activated in the athlete's heart might have an impact on cardiac function and survival in a setting of heart failure is unknown. To examine whether different changes of 14-3-3 proteins expression in physiological cardiac hypertrophy, pathological cardiac hypertrophy and chronic heart failure (CHF), we constructed mouse models of physiological cardiac hypertrophy to swim training, pathological cardiac hypertrophy to transverse aortic constriction (TAC) for 4 weeks and chronic heart failure to TAC for 16 weeks. In response to swimming training and TAC, mice showed significant increases in left ventricular diastolic posterior wall thickness (LVPWd), heart weight and normalized heart weight to body weight ratio. However, in CHF mice, LVPWd decreased, end-diastolic volume (EDV) increased and marked cardiac fibrosis was formed. Thus, pressure overload induced decompensate heart failure and eccentric hypertrophy. Moreover, 14-3-3 epsilon protein expression of hearts was increased in response to swimming training but decreased in CHF mice. However, other isoforms (beta, zeta) of 14-3-3 proteins were no obvious changes in these three models. Therefore, our results suggest that the expressions of 14-3-3 epsilon are different in physiological and pathological hypertrophy, which may provide a potential gene strategy for the treatment of heart failure.