Abstract
Background
Resveratrol 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 results
The 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 (1 g/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.
Conclusions
Resveratrol 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.
Abbreviations:
AMPK (AMP-activated protein kinase), HAT (histone acetyltransferase), HDAC (histone deacetylase), EMSA (electrophoretic mobility shift assay), IKKα (IκBα kinase), ICAM-1 (intercellular adhesion molecule-1), IL-6 (interleukin 6), MCP-1 (monocyte chemoattractant protein-1), NF-κB (nuclear factor-κB), STAT3 (signal transducer and activator of transcription 3), SOCS (suppressor of cytokine signaling), SAFE (survival activating factor enhancement), TNF-α (tumor necrosis factor-α)Keywords
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Article info
Publication history
Published online: June 29, 2012
Accepted:
June 8,
2012
Received in revised form:
June 1,
2012
Received:
March 20,
2012
Identification
Copyright
© 2012 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
