Resveratrol Attenuates Pressure Overload-Induced Cardiac Fibrosis and Diastolic Dysfunction via PTEN/AKT/Smad2/3 and NF-κB Signaling Pathways.

Abstract

Cardiac fibrosis is a key feature of cardiac remodeling. Recently, a protective role for resveratrol (RES) in pressure-overload-induced cardiac hypertrophy and contractile dysfunction has been demonstrated. However, the effect of RES on cardiac fibrosis and diastolic function in this model remains unclear. Cardiac remodeling is induced in mice by transverse aortic constriction (TAC) for 2-4 weeks. RES is administered at dose of 5 or 50mgkg-1 d-1 for 2 weeks. It is found that RES administration at 50mgkg-1 d-1 significantly attenuates TAC-induced adverse cardiac systolic and diastolic function, fibrosis, inflammation, and oxidative stress via inhibiting PTEN degradation and the downstream mediators. However, RES at 5mgkg-1 d-1 has no significant effects. RES at 50mgkg-1 d-1 also ameliorates pre-established adverse cardiac function and remodeling induced by TAC. Treatment with PTEN inhibitor VO-OHpic (10mgkg-1 d-1 ) for 2 weeks abolishes RES-mediated protective effects. Additionally, the effect of RES (100µm) on inhibition of Ang II-induced fibroblast proliferation and activation in vitro is verified. The findings provide new evidence that RES plays a critical role in the progression of cardiac fibrosis and diastolic dysfunction, and suggest that RES may be a promising therapeutic agent for cardiac fibrosis.