title: Vascular endothelial cells senescence is associated with NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation via reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP) pathway.
abstract: Endothelial dysfunction caused by endothelial cells senescence and chronic inflammation is tightly linked to the development of cardiovascular diseases. NLRP3 (NOD-like receptor family pyrin domain-containing3) inflammasome plays a central role in inflammatory response that is associated with diverse inflammatory diseases. This study explores the effects and possible mechanisms of NLRP3 inflammasome in endothelial cells senescence. Results show an increment of pro-inflammatory cytokine interleukin (IL) -1β secretion and caspase-1 activation during the senescence of endothelial cells induced by bleomycin. Moreover, secreted IL-1β promoted endothelial cells senescence through up-regulation of p53/p21 protein expression. NLRP3 inflammasome was found to mediate IL-1β secretion through the production of ROS (reactive oxygen species) during the senescence of endothelial cells. Furthermore, the association of TXNIP (thioredoxin-interacting protein) with NLRP3 induced by ROS promoted NLRP3 inflammasome activation in senescent endothelial cells. In addition, the expressions of NLRP3 inflammasome related genes, ASC (apoptosis associated speck-like protein containing a CARD), TXNIP, cleaved caspase-1 and IL-1β, were also increased in vitro and in vivo studies. These findings indicate that endothelial senescence could be mediated through ROS and NLRP3 inflammasome signaling pathways, suggesting a potential target for the prevention of endothelial senescence-related cardiovascular diseases.
authors.affiliation: Department of Cardiology, Shanghai East Hospital, and Immunology Department, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Cardiology, Shanghai East Hospital, and Immunology Department, Tongji University School of Medicine, Shanghai, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Shanghai East Hospital, and Immunology Department, Tongji University School of Medicine, Shanghai, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Shanghai East Hospital, and Immunology Department, Tongji University School of Medicine, Shanghai, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Chang
authors.affiliation: Department of Cardiology, Shanghai East Hospital, and Immunology Department, Tongji University School of Medicine, Shanghai, China.
authors.forename: Guanqun
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Shanghai East Hospital, and Immunology Department, Tongji University School of Medicine, Shanghai, China. Electronic address: daiyl@tongji.edu.cn.
authors.forename: Yalei
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001761:Bleomycin / Q000633:toxicity; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008955:Models, Cardiovascular; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C492716:Nlrp3 protein, mouse; C402202:PYCARD protein, human; C498534:Pycard protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C486715:TXNIP protein, human; C445672:Txnip protein, mouse; D001761:Bleomycin; D013879:Thioredoxins
keywords: IL-1β; NLRP3 inflammasome; ROS; Senescence; TXNIP