Lei-Xin Zou1, Chen Chen1, Xiao Yan1, Qiu-Yue Lin1, Jiao Fang1, Pang-Bo Li2, Xiao Han1, Qing-Shan Wang3, Shu-Bin Guo2, Hui-Hua Li1, Yun-Long Zhang2. 1. Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China. 2. Department of Emergency Medicine, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. 3. School of Public Health, Dalian Medical University, Dalian, 116044, China.
Abstract
SCOPE: 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. METHODS AND RESULTS: Cardiac remodeling is induced in mice by transverse aortic constriction (TAC) for 2-4 weeks. RES is administered at dose of 5 or 50 mg kg-1 d-1 for 2 weeks. It is found that RES administration at 50 mg kg-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 5 mg kg-1 d-1 has no significant effects. RES at 50 mg kg-1 d-1 also ameliorates pre-established adverse cardiac function and remodeling induced by TAC. Treatment with PTEN inhibitor VO-OHpic (10 mg kg-1 d-1 ) for 2 weeks abolishes RES-mediated protective effects. Additionally, the effect of RES (100 µm) on inhibition of Ang II-induced fibroblast proliferation and activation in vitro is verified. CONCLUSIONS: 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.
SCOPE: 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. METHODS AND RESULTS:Cardiac remodeling is induced in mice by transverse aortic constriction (TAC) for 2-4 weeks. RES is administered at dose of 5 or 50 mg kg-1 d-1 for 2 weeks. It is found that RES administration at 50 mg kg-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 5 mg kg-1 d-1 has no significant effects. RES at 50 mg kg-1 d-1 also ameliorates pre-established adverse cardiac function and remodeling induced by TAC. Treatment with PTEN inhibitor VO-OHpic (10 mg kg-1 d-1 ) for 2 weeks abolishes RES-mediated protective effects. Additionally, the effect of RES (100 µm) on inhibition of Ang II-induced fibroblast proliferation and activation in vitro is verified. CONCLUSIONS: 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.