Antioxidant Resveratrol Attenuates Cardiac Fibrosis and Reduces Matrix Metalloproteinase-2 Activity in Heart Failure Rats

Increased reactive oxygen species activate matrix metalloproteinases (MMP) playing a critical role in cardiovascular remodeling after myocardial infarction (MI). We evaluated the antioxidant effect of resveratrol (RESV) on cardiac remodeling and MMP-2 activity in heart failure (HF) rats. Wistar rats were divided into the following groups: Control; Control+RESV; HF; HF+RESV (10mg/kg/day, p.o., 4 wk). The MI was elicited by ligation of the coronary artery. After four weeks, the animals were anesthetized to evaluate the cardiac function and to collect the hearts and blood samples. Heart weight/body weight (HW/BW, mg/g) ratio and the infarct size were calculated. Histological assessment of the left ventricle was carried out with hematoxylin/eosin, and fibrosis was quantified with Masson trichrome-staining. Cardiac and plasma MMP-2 activities were determined by gel zymography. The oxidative stress was assessed measuring the thiobarbituric acid reactive substances (TBARS) from plasma. HF and HF+RESV showed similar infarct size. The HW/BW ratio increased (3.7±0.2 vs 3.8±0.2 vs 3.0±0.05). RESV improved the maximal slope of the systolic increment of left ventricular pressure in HF animals (9004±1120 vs 5849±595 vs 7181±533 mmHg/s) and reduced the end diastolic pressure (4±1 vs 18±4 vs 7±1 mmHg). HF increased TBARS, whereas RESV produced an antioxidant effect in HF+RESV group (11.2±0.9 vs 21.7±3 vs 8.2±1.4 μmol/L). HF augmented cardiac fibrosis (30,8±1,3 vs 8,8±0,5%) and myocyte hypertrophy (12,2±0,7 vs 8,8±0,3μm). RESV reduced collagen deposition in HF hearts (22,7±1,9%), but did not reduce the myocyte hypertrophy (11,7±0,6 μm). Cardiac and plasma MMP-2 activity were higher in HF animals (plasma: 1344±39 vs. 1164±47; heart: 536±54 vs. 262±18). RESV decreased plasma MMP-2 activity in control (992±27) and HF animals (1200±49) and reduced cardiac MMP-2 activity only in HF+RESV group (426±42). In conclusion, the antioxidant effect of RESV improved cardiac function and fibrosis and reduced MMP-2 levels in the heart and plasma from HF rats.