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Age-associated stresses induce an anti-inflammatory senescent phenotype in endothelial cells
Age is the greatest risk factor for cardiovascular disease. In addition, inflammation and age (senescence) have been linked at both the clinical and molecular levels. In general, senescent cells have been described as pro-inflammatory based on their senescence associated secretory phenotype (SASP)....
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883707/ https://www.ncbi.nlm.nih.gov/pubmed/24334613 |
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author | Coleman, Paul R. Chang, Garry Hutas, Gabor Grimshaw, Matthew Vadas, Mathew A. Gamble, Jennifer R. |
author_facet | Coleman, Paul R. Chang, Garry Hutas, Gabor Grimshaw, Matthew Vadas, Mathew A. Gamble, Jennifer R. |
author_sort | Coleman, Paul R. |
collection | PubMed |
description | Age is the greatest risk factor for cardiovascular disease. In addition, inflammation and age (senescence) have been linked at both the clinical and molecular levels. In general, senescent cells have been described as pro-inflammatory based on their senescence associated secretory phenotype (SASP). However, we have previously shown that senescence induced by overexpression of SENEX (or ARHGAP18), in endothelial cells results in an anti-inflammatory phenotype. We have investigated, at the individual cellular level, the senescent phenotype of endothelial cells following three of the chief signals associated with ageing; oxidative stress, disturbed flow and hypoxia. All three stimuli induce senescence and, based on neutrophil adhesion and expression of the adhesion molecules E-selectin and VCAM-1, a population of senescent cells is seen that is resistant to inflammatory stimuli and thus we define as anti-inflammatory. The proportion of anti-inflammatory cells increases with time but remains stable at approximately 50% by eight days after induction of senescence, suggesting that these are stable phenotypes of endothelial cell senescence. Similar to other senescent cell types, p38MAPK blockade inhibits the development of the pro-inflammatory phenotype but unique to EC, there is a corresponding increase in the number of anti-inflammatory senescent cells. Thus stress-induced senescent endothelial cells display a mosaic of inflammatory phenotypes. The anti-inflammatory population suggests that senescent endothelial cells may have an unique protective role, to inhibit uncontrolled proliferation and to limit the local inflammatory response. |
format | Online Article Text |
id | pubmed-3883707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-38837072014-01-13 Age-associated stresses induce an anti-inflammatory senescent phenotype in endothelial cells Coleman, Paul R. Chang, Garry Hutas, Gabor Grimshaw, Matthew Vadas, Mathew A. Gamble, Jennifer R. Aging (Albany NY) Research Paper Age is the greatest risk factor for cardiovascular disease. In addition, inflammation and age (senescence) have been linked at both the clinical and molecular levels. In general, senescent cells have been described as pro-inflammatory based on their senescence associated secretory phenotype (SASP). However, we have previously shown that senescence induced by overexpression of SENEX (or ARHGAP18), in endothelial cells results in an anti-inflammatory phenotype. We have investigated, at the individual cellular level, the senescent phenotype of endothelial cells following three of the chief signals associated with ageing; oxidative stress, disturbed flow and hypoxia. All three stimuli induce senescence and, based on neutrophil adhesion and expression of the adhesion molecules E-selectin and VCAM-1, a population of senescent cells is seen that is resistant to inflammatory stimuli and thus we define as anti-inflammatory. The proportion of anti-inflammatory cells increases with time but remains stable at approximately 50% by eight days after induction of senescence, suggesting that these are stable phenotypes of endothelial cell senescence. Similar to other senescent cell types, p38MAPK blockade inhibits the development of the pro-inflammatory phenotype but unique to EC, there is a corresponding increase in the number of anti-inflammatory senescent cells. Thus stress-induced senescent endothelial cells display a mosaic of inflammatory phenotypes. The anti-inflammatory population suggests that senescent endothelial cells may have an unique protective role, to inhibit uncontrolled proliferation and to limit the local inflammatory response. Impact Journals LLC 2013-12-12 /pmc/articles/PMC3883707/ /pubmed/24334613 Text en Copyright: © 2013 Coleman et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Research Paper Coleman, Paul R. Chang, Garry Hutas, Gabor Grimshaw, Matthew Vadas, Mathew A. Gamble, Jennifer R. Age-associated stresses induce an anti-inflammatory senescent phenotype in endothelial cells |
title | Age-associated stresses induce an anti-inflammatory senescent phenotype in endothelial cells |
title_full | Age-associated stresses induce an anti-inflammatory senescent phenotype in endothelial cells |
title_fullStr | Age-associated stresses induce an anti-inflammatory senescent phenotype in endothelial cells |
title_full_unstemmed | Age-associated stresses induce an anti-inflammatory senescent phenotype in endothelial cells |
title_short | Age-associated stresses induce an anti-inflammatory senescent phenotype in endothelial cells |
title_sort | age-associated stresses induce an anti-inflammatory senescent phenotype in endothelial cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883707/ https://www.ncbi.nlm.nih.gov/pubmed/24334613 |
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