title: Suppression of NADPH oxidase attenuates hypoxia-induced dysfunctions of endothelial progenitor cells.
abstract: NADPH oxidases (NOX) - derived reactive oxygen species (ROS) contribute to oxidative injury in hypoxia-induced pulmonary arterial hypertension. This study aims to evaluate the status of NOX in endothelial progenitor cells (EPCs) under hypoxic condition and to determine whether NOX inhibitors could attenuate hypoxia-induced dysfunctions of EPCs. EPCs were isolated from peripheral blood of SD rats and subjected to hypoxia (O2/N2/CO2, 1/94/5) for 24 h. The cells were collected for β-galactosidase or Hoechst staining, or for functional analysis (migration, adhesion and tube formation). The NOX expression, activity and H2O2content in EPCs were measured. The results showed that hypoxia treatment promoted EPC senescence and apoptosis, accompanied by the deteriorated functions of EPCs (the reduced abilities in adhesion, migration and tube formation), as well as an increase in NOX2 and NOX4 expression, NOX activity and H2O2production, these phenomena were attenuated by NOX inhibitors. Furthermore, administration of catalase could also improve the functions of hypoxia-treated EPCs. Based on these observations, we conclude that NOX-derived ROS contributes to the dysfunctions of EPCs under hypoxic condition. Thus, suppression of NOX may provide a novel strategy to improve endothelial functions in hypoxia-relevant diseases.
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China.
authors.forename: Kai-Di
authors.initials: KD
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China.
authors.forename: Jing-Jie
authors.initials: JJ
authors.lastname: Peng
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, 410013, China.
authors.forename: Xiu-Ju
authors.initials: XJ
authors.lastname: Luo
authors.affiliation: Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, 410011, Changsha, China.
authors.forename: Chengming
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Cardiovascular Surgery, The Second Xiangya Hospital, Central South University, 410011, Changsha, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China.
authors.forename: Jin-Fu
authors.initials: JF
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China. Electronic address: Junpeng@csu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D017209:Apoptosis; D002374:Catalase / Q000737:chemistry; D002448:Cell Adhesion; D015687:Cell Hypoxia; D002465:Cell Movement; D016922:Cellular Senescence; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000737:chemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010641:Phenotype; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C070295:catalase-polyethylene glycol; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D002374:Catalase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; D001616:beta-Galactosidase
keywords: Dysfunction; Endothelial progenitor cells; Hypoxia; NADPH oxidase; Reactive oxygen species