Role of melatonin, melatonin receptors and STAT3 in the cardioprotective effect of chronic and moderate consumption of red wine

• Published in: Biochemical and biophysical research communications Vol. 465; no. 4; pp. 719 - 724
• Main Authors: Lamont, Kim, Nduhirabandi, Frederic, Adam, Tasneem, Thomas, D. Paul, Opie, Lionel H., Lecour, Sandrine
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02-10-2015
• Subjects: Animals; Cardioprotection; Cardiotonic Agents - administration & dosage; Ischemia-reperfusion; Male; Melatonin; Melatonin - administration & dosage; Melatonin - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Infarction - diet therapy; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Prazosin - pharmacology; Rats; Rats, Wistar; Receptor, Melatonin, MT1 - antagonists & inhibitors; Receptor, Melatonin, MT1 - metabolism; Receptor, Melatonin, MT2 - antagonists & inhibitors; Receptor, Melatonin, MT2 - metabolism; Receptors, Melatonin - antagonists & inhibitors; Receptors, Melatonin - metabolism; Receptors, Tumor Necrosis Factor, Type II - deficiency; Receptors, Tumor Necrosis Factor, Type II - genetics; Red wine; SAFE pathway; STAT3 Transcription Factor - antagonists & inhibitors; STAT3 Transcription Factor - deficiency; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Tryptamines - pharmacology; Tyrphostins - pharmacology; Vitaceae; Wine - analysis; Ischemia-reperfusion; Melatonin; Cardioprotection; Red wine; SAFE pathway
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.08.064

We have recently discovered that melatonin, given acutely and directly to the isolated heart at the concentration found in wine, confers cardioprotection against ischemia-reperfusion (I/R). However, whether the presence of melatonin in wine contributes to the cardioprotective effect of chronic and moderate consumption of wine and its signalling mechanisms of protection are unknown. We therefore used both in vivo and in vitro models of I/R to investigate whether the presence of melatonin in red wine may contribute to the cardioprotective effect of chronic and moderate consumption of red wine. Wistar rats and C57black6 mice (WT) received drinking water supplemented daily with a moderate amount of red wine or melatonin given at the concentration found in the red wine. Rats were also pretreated with luzindole, a specific inhibitor of melatonin receptors 1 and 2 (2.3 mg/kg/day, intraperitoneally) or prazosin, a specific inhibitor of melatonin receptor type 3 (2.5 mg/kg/day, intraperitoneally). After 14 days, hearts were subjected to I/R in vivo or ex vivo. Red wine reduced the infarct size in both rats and WT mice (p < 0.001). Luzindole did not affect wine-induced cardioprotection, while prazosin reduced the infarct sparing effect of red wine (p < 0.05). Furthermore, red wine or melatonin failed to protect tumor necrosis factor alpha (TNF) receptor 2 knockout or cardiomyocyte specific signal transducer and activator of transcription 3 (STAT3) deficient mice (n.s. vs. control). Our novel findings suggest that the presence of melatonin in red wine contributes to the cardioprotective effect of chronic and moderate consumption of red wine against lethal I/R injuries. This effect is most likely mediated, at least in part, via melatonin receptor 3 and the activation of TNF and STAT3, both key players of the prosurvival and well described SAFE pathway.
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•Moderate consumption of red wine protects against in vivo myocardial infarction.•Melatonin at concentration found in wine confers cardioprotection in vivo.•Red wine-induced cardioprotection is attenuated with melatonin receptor 3 inhibitors.•Red wine-induced cardioprotection requires activation of the STAT3 pathway.