title: Age-associated stresses induce an anti-inflammatory senescent phenotype in endothelial cells.
abstract: 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 ofSENEX (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.
authors: Centre for the Endothelium, Vascular Biology Program, Centenary Institute, Locked Bag #6, Newtown NSW, Australia and the University of Sydney, NSW, Australia.
authors: Paul R
authors: PR
authors: Coleman
authors: Garry
authors: G
authors: Chang
authors: Gabor
authors: G
authors: Hutas
authors: Matthew
authors: M
authors: Grimshaw
authors: Mathew A
authors: MA
authors: Vadas
authors: Jennifer R
authors: JR
authors: Gamble
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006861:Hydrogen Peroxide; D007249:Inflammation / Q000378:metabolism*; D018384:Oxidative Stress; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D019010:Vascular Cell Adhesion Molecule-1; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases