| Novel control of cAMP-regulated transcription in vascular endothelial cells. | |
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MedLine Citation:
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PMID: 22260656 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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. |
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Authors:
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Gillian R Milne; Timothy M Palmer; Stephen J Yarwood |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Biochemical Society transactions Volume: 40 ISSN: 1470-8752 ISO Abbreviation: Biochem. Soc. Trans. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-01-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7506897 Medline TA: Biochem Soc Trans Country: England |
Other Details:
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Languages: eng Pagination: 1-5 Citation Subset: IM |
Affiliation:
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*Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, U.K. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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