• Xavier Palomer, Eva Capdevila-Busquets, David Alvarez-Guardia, Emma Barroso, Mercè Pallàs, Antoni Camins, Mercy M Davidson, Ana Planavila, Francesc Villarroya, and Manuel Vázquez-Carrera.
• Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona and IBUB, Institut de Biomedicina de la Universitat de Barcelona, 643 Diagonal, E-08028 Barcelona, Spain.
• Int. J. Cardiol. 2013 Sep 10; 167 (6): 2507-16.

BackgroundResveratrol is a grape polyphenol that prevents cardiac hypertrophy and protects the heart from ischemic injury, metabolic dysregulation, and inflammatory processes in several murine models.Methods And ResultsThe aim of this study was to investigate the effects of resveratrol on the inflammatory processes in human cardiac AC16 cells in order to gain a better understanding of its cardioprotective mechanisms in the human heart. Resveratrol induced the DNA-binding activity of the pro-inflammatory transcription factor NF-κB in AC16 cells, and exacerbated the increase caused by tumor necrosis factor-α (TNF-α). In accordance with this, resveratrol increased the expression of the pro-inflammatory genes ICAM-1 (intercellular adhesion molecule-1) and TNF-α. In contrast, resveratrol decreased the expression of pro-inflammatory genes IL-6 (interleukin-6) and MCP-1 (monocyte chemoattractant protein-1). Likewise, resveratrol also induced inflammation in rat neonatal cardiomyocytes, and in the heart of mice fed a standard chow diet supplemented with resveratrol (1g/kg diet) for four months. Western-blot analyses revealed that NF-κB p65 subunit levels were upregulated in an IκB-dependent manner in the nuclei of resveratrol-treated human cardiac cells. Finally, resveratrol activated the signal transducer and activator of transcription 3 (STAT3) signaling and induced the expression of its anti-apoptotic downstream effector Bcl-xL, both involved in the cardioprotective survival activating factor enhancement (SAFE) pathway.ConclusionsResveratrol enhanced NF-κB activity in human and murine cardiac cells, in a process that coincided with the activation of STAT3 and anti-apoptotic downstream effectors. Therefore, activation of the SAFE pathway by resveratrol might be involved in the cardioprotective effects of this compound.Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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