Suppressor of cytokine signalling 3 (SOCS3) is a potent inhibitor of pro-inflammatory pathways involved inatherogenesis and the development of neo-intimal hyperplasia (NIH), which contributes to the in-stent re-stenosisresponsible for the failure of percutaneous coronary intervention (PCI) procedures. We have shown that cyclic AMPsensor EPAC1 triggers induction of the SOCS3 gene in vascular endothelial cells (VECs), thereby attenuatinginterleukin 6 (IL-6)-mediated pro-inflammatory signalling. We propose that EPAC1 localisation to the nuclear porecontrols cyclic AMP-mediated activation of a C/EBPβ/c-Jun transcriptional complex, leading to SOCS3 induction andsuppression of pro-inflammatory signalling. Future work in this area will involve an integrated approach to determinethe wider significance of the EPAC1-C/EBPβ/c-Jun pathway in controlling human VEC function and identify newtherapeutic targets for management of chronic inflammation in vascular settings.
Palmer, T. M., & Yarwood, S. J. (2015). Regulation of anti-inflammatory gene expression in vascular endothelial cells by EPAC1. Journal of Cell Signaling, 1(1), . https://doi.org/10.4172/jcs.1000103