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CARDIOVASCULAR

Effects of Resveratrol (trans-3,5,4'-Trihydroxystilbene) Treatment on Cardiac Remodeling following Myocardial Infarction

Research Center (B.B., A.M., R.C., H.G., F.P., J.-C.T., S.N.) and Department of Physiology (A.C.), Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada; and Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada (B.B., N.E., T.E.H., S.N.)

Resveratrol (RES; trans-3,5,4'-trihydroxystilbene) has been shown to improve health and slow the progression of disease in various models. Several cardioprotective mechanisms have been identified including antioxidant, anti-inflammatory, and antifibrotic actions. Each of these actions is thought to have the ability to attenuate the pathophysiology underlying the deleterious cardiac structural remodeling that results from acute myocardial infarction (MI). Therefore, we evaluated the effect of resveratrol treatment on the progression of cardiac remodeling after MI. Four groups of rats (sham, n = 6; sham + RES, n = 21; MI, n = 26; MI + RES, n = 24) were treated for 13 weeks, starting 7 days before ligation of the left anterior descending coronary artery. Serial transthoracic echocardiography revealed that resveratrol had no effect on MI-induced left-ventricular and left-atrial dilatation or reduction in left-ventricular fractional shortening. Consistent with these findings, resveratrol did not improve the deterioration of hemodynamic function or reduce infarct size at 12 weeks post-MI. Resveratrol-treated animals did, however, show preserved cardiac contractile reserve in response to dobutamine administration. Radioligand binding revealed that MI reduced -adrenergic receptor density. Resveratrol administration increased -adrenoceptor density, so that resveratrol-treated MI rats had -adrenoceptor densities similar to normal rats. Real-time reverse transcription-polymerase chain reaction revealed that MI-induced changes in sarcoplasmic reticulum Ca²⁺-ATPase 2 and transforming growth factor -1 expression were unaltered by resveratrol, whereas MI-induced increases in atrial natriuretic factor (ANF) and connective tissue growth factor (CTGF) expression were attenuated. Resveratrol treatment does not improve cardiac remodeling and global hemodynamic function post-MI but does preserve contractile reserve and attenuate ANF and CTGF up-regulation.

Address correspondence to: Stanley Nattel, 5000 Belanger St. E., Montreal, Quebec H1T 1C8, Canada. E-mail: stanley.nattel{at}icm-mhi.org