Regulation of anti-inflammatory gene expression in vascular endothelial cells by EPAC1

Palmer, T. P. and Yarwood, S. J. (2015) Regulation of anti-inflammatory gene expression in vascular endothelial cells by EPAC1. Journal of Cell Signaling, 1(1), 1000103. (doi: 10.4172/jcs.1000103)

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Suppressor of cytokine signalling 3 (SOCS3) is a potent inhibitor of pro-inflammatory pathways involved in atherogenesis and the development of neo-intimal hyperplasia (NIH), which contributes to the in-stent re-stenosis responsible for the failure of percutaneous coronary intervention (PCI) procedures. We have shown that cyclic AMP sensor EPAC1 triggers induction of the SOCS3 gene in vascular endothelial cells (VECs), thereby attenuating interleukin 6 (IL-6)-mediated pro-inflammatory signalling. We propose that EPAC1 localisation to the nuclear pore controls cyclic AMP-mediated activation of a C/EBPβ/c-Jun transcriptional complex, leading to SOCS3 induction and suppression of pro-inflammatory signalling. Future work in this area will involve an integrated approach to determine the wider significance of the EPAC1-C/EBPβ/c-Jun pathway in controlling human VEC function and identify new therapeutic targets for management of chronic inflammation in vascular settings.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Yarwood, Dr Stephen and Palmer, Dr Timothy
Authors: Palmer, T. P., and Yarwood, S. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Journal of Cell Signaling
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Journal of Cell Signaling 1(1):1000103
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
683671Regulation of Anti-inflammatory Gene Expression in Vascular Endothelial Cells by EPAC1Stephen YarwoodBritish Heart Foundation (BHF)PG/15/15/31316RI MOLECULAR CELL & SYSTEMS BIOLOGY