title: Ambient fine particulate matter induces apoptosis of endothelial progenitor cells through reactive oxygen species formation.
abstract: OBJECTIVE
  Bone marrow (BM)-derived endothelial progenitor cells (EPCs) play a critical role in angiogenesis and vascular repair. Some environmental insults, like fine particulate matter (PM) exposure, significantly impair cardiovascular functions. However, the mechanisms for PM-induced adverse effects on cardiovascular system remain largely unknown. The present research was to study the detrimental effects of PM on EPCs and explore the potential mechanisms.
  
  
  METHODS
  PM was intranasal-distilled into male C57BL/6 mice for one month. Flow cytometry was used to measure the number of EPCs, apoptosis level of circulating EPCs and intracellular reactive oxygen species (ROS) formation. Serum TNF-α and IL-1β were measured using ELISA. To determine the role of PM-induced ROS in EPC apoptosis, PM was co-administrated with the antioxidant N-acetylcysteine (NAC) in wild type mice or used in a triple transgenic mouse line (TG) with overexpression of antioxidant enzyme network (AON) composed of superoxide dismutase (SOD)1, SOD3, and glutathione peroxidase (Gpx-1) with decreased in vivo ROS production.
  
  
  RESULTS
  PM treatment significantly decreased circulating EPC population, promoted apoptosis of EPCs in association with increased ROS production and serum TNF-α and IL-1β levels, which could be effectively reversed by either NAC treatment or overexpression of AON.
  
  
  CONCLUSIONS
  PM exposure significantly decreased circulating EPCs population due to increased apoptosis via ROS formation in mice.
authors.affiliation: Dorothy M. Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Cui
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xie
authors.forename: Fengpeng
authors.initials: F
authors.lastname: Jia
authors.forename: Jianfeng
authors.initials: J
authors.lastname: He
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.forename: Minghuan
authors.initials: M
authors.lastname: Fu
authors.forename: Hong
authors.initials: H
authors.lastname: Hao
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Jason Z
authors.initials: JZ
authors.lastname: Liu
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cowan
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052638:Particulate Matter / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D053583:Interleukin-1beta; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D005979:Glutathione Peroxidase; C000606291:Sod1 protein, mouse; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000111:Acetylcysteine