Novel control of cAMP-regulated transcription in vascular endothelial cells
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-...
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Published in | Biochemical Society transactions Vol. 40; no. 1; p. 1 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
England
01.02.2012
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Subjects | |
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Abstract | 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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AbstractList | 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. |
Author | Palmer, Timothy M Milne, Gillian R Yarwood, Stephen J |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/22260656$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_1021_es3050967 crossref_primary_10_1186_s12959_020_00240_z crossref_primary_10_1016_j_lfs_2013_11_012 crossref_primary_10_1016_j_jtcms_2016_07_003 crossref_primary_10_1016_j_lfs_2019_02_014 crossref_primary_10_1111_cns_13880 crossref_primary_10_1016_j_ccm_2013_09_007 crossref_primary_10_1016_j_cellsig_2012_04_015 crossref_primary_10_1152_physrev_00025_2017 crossref_primary_10_3390_biom11081079 crossref_primary_10_1152_ajpendo_00511_2018 |
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SubjectTerms | CCAAT-Enhancer-Binding Protein-beta - metabolism CCAAT-Enhancer-Binding Protein-delta - metabolism Cells, Cultured Cyclic AMP - metabolism Endothelium, Vascular - metabolism Endothelium, Vascular - pathology Gene Expression Regulation Guanine Nucleotide Exchange Factors - metabolism Human Umbilical Vein Endothelial Cells - metabolism Humans Inflammation - metabolism Signal Transduction Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins - genetics Suppressor of Cytokine Signaling Proteins - metabolism Transcription, Genetic |
Title | Novel control of cAMP-regulated transcription in vascular endothelial cells |
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