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标题：Age-associated stresses induce an anti-inflammatory senescent phenotype in endothelial cells
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作者：Paul R. Coleman ; Garry Chang ; Gabor Hutas 等
期刊名称：Aging
出版年度：2013
卷号：5
期号：12
页码：913-924
出版社：U.S.Department of Health & Human Service
摘要：Age. is. the. greatest. risk. factor. for. cardiovascular. disease..In. addition,. inflammation. and.age. (senescence). havebeen. linked.at.both.the.clinical.and.molecular.levels.. In.general,.senescent.cells.have. been.described.as.pro©\inflammatorybased. on. their. senescence. associated. secretory. phenotype. (SASP).. However,. we.have. previously. shown.that. senescenceinduced. by. overexpression. of. SENEX. (or. ARHGAP18),. in. endothelial. cells. results. in. an. anti©\inflammatory. phenotype.. Wehave.investigated,.at.the.individual.cellular.level,.the.senescent.phenotype.of.endothelial.cells.following.three.of.the.chiefsignals.associated.with.ageing;.oxidative.stress,.disturbed.flow.and.hypoxia..All.three.stimuli.induce.senescence.and,.basedon.neutrophil.adhesion.and.expression.of.the.adhesion.molecules.E©\selectin.and.VCAM©\1,.a.population.of.senescent.cells.isseen. 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. ofsenescence,. suggesting. that. these. are. stable. phenotypes. of. endothelial. cell. senescence.. Similar. to. other. senescent. celltypes,. p38MAPK. blockade. inhibits. the. development. of. the. pro©\inflammatory. phenotype. but. unique. to. EC,. there. is. acorresponding. increase. in. the. number. of. anti©\inflammatory. senescent. cells.. Thus. stress©\induced. senescent. endothelialcells.display.a.mosaic.of.inflammatory.phenotypes.. The. anti©\inflammatory.population.suggests.that.senescent.endothelialcells.may.have.an.unique.protective.role,.to.inhibit.uncontrolled.proliferation.and.to.limit.the.local.inflammatory.response
关键词：senescence;.endothelial.cells;.inflammation;.ARHGAP18;.SENEX;.ageing