Cardioprotective Effect of (Z)-2-Acetoxy-3-(3,4-Dihydroxyphenyl) Acrylic Acid: Inhibition of Apoptosis in Cardiomyocytes

BACKGROUND: Although many studies have been performed to elucidate the molecular mechanisms of heart failure, an effective pharmacological therapy to protect cardiac tissues from severe loss of contractile function associated with heart failure after acute myocardial infarction (MI) has yet to be developed. METHODS: We examined the cardioprotective effects of (Z)-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid, a new compound with potent antioxidant and antiapoptotic activities in a rat model of heart failure. (Z)-2-Acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid was systemically delivered to rats 6 weeks after MI at different doses (15, 30, and 60 mg/kg). Cardiac function was assessed by hemodynamic measurements. The expression of proinflammatory cytokines, apoptosis-related molecules, and markers of adverse ventricular remodeling was measured using RT-PCR and Western blot. RESULTS: Treatment with (Z)-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid significantly improved cardiac function, in particular by increasing dP/dt. Simultaneously, the expression of the proinflammatory cytokines TNF-α and IL-1β was markedly reduced in the treatment group compared with the MI group. In addition, (Z)-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid-treated tissues displayed decreased expression of Bax, caspase-3, and caspase-9 and increased expression of Bcl-2, which was in part due to the promotion of Akt phosphorylation. CONCLUSION: These data demonstrated that (Z)-2-acetoxy-3-(3,4-dihydroxyphenyl) acrylic acid possesses potent cardioprotective effects against cardiac injury in a rat model of heart failure, which is mediated, at least in part, by suppression of the inflammatory and cell apoptosis responses.