Novel control of cAMP-regulated transcription in vascular endothelial cells

Milne, G. R., Palmer, T. M. and Yarwood, S. J. (2012) Novel control of cAMP-regulated transcription in vascular endothelial cells. Biochemical Society Transactions, 40(1), pp. 1-5. (doi: 10.1042/BST20110606)

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Chronic inflammatory diseases, such as atherosclerosis, are a major cause of death and disability in the developed world. In this respect, although cholesterol obviously plays a predominant role in atherosclerosis, targeting inflammation at lesion sites may be just as important. Indeed, elevated IL-6 (interleukin 6) levels are as strongly associated with coronary heart disease as increased cholesterol. We have been investigating novel cAMP-regulated pathways that combat the action of pro-inflammatory cytokines, such as IL-6 and leptin, in the VECs (vascular endothelial cells) of the circulatory system. In this respect, we have begun to unravel new molecular mechanisms by which the cAMP/Epac1 (exchange protein directly activated by cAMP 1)/Rap1 pathway can initiate a rigorous programme of protective anti-inflammatory responses in VECs. Central to this is the coupling of cAMP elevation to the mobilization of two C/EBP (CCAAT/enhancer-binding protein) family transcription factors, resulting in the induction of the SOCS3 (suppressor of cytokine signalling 3) gene, which attenuates pro-inflammatory cytokine signalling in VECs. These novel 'protective' mechanisms of cAMP action will inform the development of the next generation of pharmaceuticals specifically designed to combat endothelial inflammation associated with cardiovascular disease.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Yarwood, Dr Stephen and Palmer, Dr Timothy and Milne, Dr Gillian
Authors: Milne, G. R., Palmer, T. M., 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 Life Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Biochemical Society Transactions
Publisher:Portland Press Ltd.
ISSN (Online):1470-8752
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
498581EPAC1 and ERK-dependent activation of C/EBP transcription factors: a new cyclic AMP-activated anti-inflammatory gene expression module in vascular endothelial cellsTimothy PalmerBritish Heart Foundation (BHF)PG/08/125/26415Institute of Cardiovascular and Medical Sciences
528251The Role of EPAC1-regulated Protein Kinase C Isoforms in Mediating C/EBPdelta -dependent, Anti-inflammatory Actions of Cyclic AMP in Vascular Endothelial CellsStephen YarwoodBritish Heart Foundation (BHF)PG/10/026/28303Institute of Molecular Cell and Systems Biology