title: Decreased and dysfunctional circulating endothelial progenitor cells in patients with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  It has been widely demonstrated that endothelial progenitor cells are involved in several diseases and that they have therapeutic implications. In order to define the altered pulmonary vascular homeostasis in chronic obstructive pulmonary disease, we sought to observe the level and functions of circulating endothelial progenitor cells in patients with chronic obstructive pulmonary disease.
  
  
  METHODS
  The total study population included 20 patients with chronic obstructive pulmonary disease and 20 control subjects. The number of circulating endothelial progenitor cells (CD34(+)/CD133(+)/VEGFR-2(+) cells) was counted by flow cytometry. Circulating endothelial progenitor cells were also cultured in vitro and characterized by uptake of DiIacLDL, combining with UEA-I, and expression of von Willebrand factor and endothelial nitric oxide synthase. Adhesion, proliferation, production of nitric oxide, and expression of endothelial nitric oxide synthase and phosphorylated-endothelial nitric oxide synthase were detected to determine functions of circulating endothelial progenitor cells in patients with chronic obstructive pulmonary disease.
  
  
  RESULTS
  The number of circulating endothelial progenitor cells in the chronic obstructive pulmonary disease group was lower than in the control group: (0.54 ± 0.16)% vs. (1.15 ± 0.57)%, P < 0.05. About 80% of adherent peripheral blood mononuclear cells cultured in vitro were double labeled with Dil-acLDL and UEA-1. The 92% and 91% of them were positive for von Willebrand factor and endothelial nitric oxide synthase, respectively. Compared with the control, there were significantly fewer adhering endothelial progenitor cells in chronic obstructive pulmonary disease patients: 18.7 ± 4.8/field vs. 45.0 ± 5.9/field, P < 0.05. The proliferation assay showed that the proliferative capacity of circulating endothelial progenitor cells from chronic obstructive pulmonary disease patients was significantly impaired: 0.135 ± 0.038 vs. 0.224 ± 0.042, P < 0.05. Furthermore, nitric oxide synthase (112.06 ± 10.00 vs. 135.41 ± 5.38, P < 0.05), phosphorylated endothelial nitric oxide synthase protein expression (88.89 ± 4.98 vs. 117.98 ± 16.49, P < 0.05) and nitric oxide production ((25.11 ± 5.27) µmol/L vs. (37.72 ± 7.10) µmol/L, P < 0.05) were remarkably lower in endothelial cells from the chronic obstructive pulmonary disease group than the control.
  
  
  CONCLUSIONS
  Circulating endothelial progenitor cells were decreased and functionally impaired in patients with chronic obstructive pulmonary disease.
authors.affiliation: Department of Geriatrics, Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.forename: Ye
authors.initials: Y
authors.lastname: Gan
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: He
authors.forename: Hong
authors.initials: H
authors.lastname: Luo
authors.forename: Shan
authors.initials: S
authors.lastname: Cai
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Xiang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
mesh_terms: D000071916:AC133 Antigen; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D040301:Vascular Endothelial Growth Factor Receptor-2