Resveratrol as a new inhibitor of immunoproteasome prevents PTEN degradation and attenuates cardiac hypertrophy after pressure overload

Sustained cardiac hypertrophy can be a primary reason for heart failure (HF) and dying. Recent surveys have proven that resveratrol (RES) exerts a security role in hypertrophic illnesses. However, the molecular mechanisms involved aren’t fully elucidated. In this particular study, cardiac hypertrophic remodeling in rodents were established by pressure overload brought on by transverse aortic constriction (TAC). Cardiac function was evaluated by echocardiography and invasive pressure-volume analysis. Cardiomyocyte size was detected by wheat germ agglutinin staining. The protein and gene expressions of signaling mediators and hypertrophic markers were examined. Our results shown that administration of RES significantly hidden pressure overload-caused cardiac hypertrophy, fibrosis and apoptosis and improved in vivo heart function in rodents. RES also reversed pre-established hypertrophy and restoring contractile disorder brought on by chronic pressure overload. In addition, RES treatment blocked TAC-caused increase of immunoproteasome activity and catalytic subunit expression (ß1i, ß2i and ß5i), which inhibited PTEN degradation therefore leading to inactivation of AKT/mTOR and activation of AMPK signals. Further, blocking PTEN with the specific VO-Ohpic inhibitor VO-Ohpic significantly attenuated RES inhibitory effect on cardiomyocyte hypertrophy in vivo plus vitro. Taken together, our data declare that RES can be a novel inhibitor of immunoproteasome activity, and may represent a good therapeutic agent to deal with hypertrophic illnesses.