Document Detail

Novel control of cAMP-regulated transcription in vascular endothelial cells.
MedLine Citation:
PMID:  22260656     Owner:  NLM     Status:  MEDLINE    
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.
Gillian R Milne; Timothy M Palmer; Stephen J Yarwood
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical Society transactions     Volume:  40     ISSN:  1470-8752     ISO Abbreviation:  Biochem. Soc. Trans.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-20     Completed Date:  2012-05-18     Revised Date:  2014-10-07    
Medline Journal Info:
Nlm Unique ID:  7506897     Medline TA:  Biochem Soc Trans     Country:  England    
Other Details:
Languages:  eng     Pagination:  1-5     Citation Subset:  IM    
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MeSH Terms
CCAAT-Enhancer-Binding Protein-beta / metabolism
CCAAT-Enhancer-Binding Protein-delta / metabolism
Cells, Cultured
Cyclic AMP / metabolism*
Endothelium, Vascular / metabolism,  pathology
Gene Expression Regulation
Guanine Nucleotide Exchange Factors / metabolism*
Human Umbilical Vein Endothelial Cells / metabolism*
Inflammation / metabolism
Signal Transduction
Suppressor of Cytokine Signaling Proteins / genetics,  metabolism
Transcription, Genetic*
Grant Support
BB/D015324/1//Biotechnology and Biological Sciences Research Council; PG/08/125//British Heart Foundation; PG/08/125/26415//British Heart Foundation; PG/10/026/28303//British Heart Foundation; PG/10/26/28303//British Heart Foundation
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Protein-beta; 0/CEBPB protein, human; 0/CEBPD protein, human; 0/Guanine Nucleotide Exchange Factors; 0/RAPGEF3 protein, human; 0/SOCS3 protein, human; 0/Suppressor of Cytokine Signaling Proteins; 142662-43-9/CCAAT-Enhancer-Binding Protein-delta; E0399OZS9N/Cyclic AMP

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