title: Brief secondhand smoke exposure depresses endothelial progenitor cells activity and endothelial function: sustained vascular injury and blunted nitric oxide production.
abstract: OBJECTIVE
  This study sought to analyze the effects of acute secondhand smoke (SHS) exposure on the number and function of endothelial progenitor cells (EPCs) over 24 h.
  
  
  BACKGROUND
  Secondhand smoke increases the risk of vascular disease and is a major public health concern, but the mechanism(s) of action are not fully understood.
  
  
  METHODS
  Healthy nonsmokers (age SEM 30.3 +/- 1.3 years, n = 10) were exposed to 30 min of SHS yielding cotinine levels commonly observed in passive smokers and to smokefree air on 2 separate days. Measurements were taken before exposure (baseline), immediately after (0 h), and at 1 h, 2.5 h, and 24 h after. The EPCs (CD133(+)/KDR(+), CD34(+)/KDR(+)) and endothelial microparticles (EMPs: CD31(+)/CD41(-), CD144(+), CD62e(+)) were determined in blood using flow cytometry. The EPC chemotaxis toward vascular endothelial growth factor was measured. Endothelial function was assessed as flow-mediated dilation (FMD) using ultrasound.
  
  
  RESULTS
  Secondhand smoke exposure increased EPCs and plasma vascular endothelial growth factor and completely abolished EPC chemotaxis during 24 h after exposure. Secondhand smoke increased EMPs and decreased FMD. Although FMD returned to baseline at 2.5 h, EMPs and vascular endothelial growth factor levels remained elevated at 24 h, suggesting endothelial activation and injury with functional impairment of the vascular endothelium. Exposure to smokefree air had no effect. Incubation of EPCs from nonexposed subjects with plasma isolated from SHS-exposed subjects in vitro decreased chemotaxis by blockade of vascular endothelial growth factor-stimulated nitric oxide production.
  
  
  CONCLUSIONS
  Brief exposure to real-world levels of SHS leads to sustained vascular injury characterized by mobilization of dysfunctional EPCs with blocked nitric oxide production. Our results suggest that SHS not only affects the vascular endothelium, but also the function of EPCs.
authors.affiliation: Division of Cardiology, Department of Medicine, University of California, San Francisco, California 94143-0103, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.forename: Nicolas
authors.initials: N
authors.lastname: Amabile
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Lee
authors.forename: Wendy May
authors.initials: WM
authors.lastname: Real
authors.forename: Suzaynn F
authors.initials: SF
authors.lastname: Schick
authors.forename: David
authors.initials: D
authors.lastname: Lao
authors.forename: Maelene L
authors.initials: ML
authors.lastname: Wong
authors.forename: Sarah
authors.initials: S
authors.lastname: Jahn
authors.forename: Franca S
authors.initials: FS
authors.lastname: Angeli
authors.forename: Petros
authors.initials: P
authors.lastname: Minasi
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Springer
authors.forename: S Katharine
authors.initials: SK
authors.lastname: Hammond
authors.forename: Stanton A
authors.initials: SA
authors.lastname: Glantz
authors.forename: William
authors.initials: W
authors.lastname: Grossman
authors.forename: John R
authors.initials: JR
authors.lastname: Balmes
authors.forename: Yerem
authors.initials: Y
authors.lastname: Yeghiazarians
mesh_terms: D000328:Adult; D002633:Chemotaxis; D003367:Cotinine / Q000097:blood; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology*; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D013234:Stem Cells / Q000187:drug effects; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D014028:Tobacco Smoke Pollution; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D003367:Cotinine