Brief secondhand smoke exposure depresses endothelial progenitor cells activity and endothelial function: sustained vascular injury and blunted nitric oxide production.
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.
Heiss
Christian
C
Division of Cardiology, Department of Medicine, University of California, San Francisco, California 94143-0103, USA.
Amabile
Nicolas
N
Lee
Andrew C
AC
Real
Wendy May
WM
Schick
Suzaynn F
SF
Lao
David
D
Wong
Maelene L
ML
Jahn
Sarah
S
Angeli
Franca S
FS
Minasi
Petros
P
Springer
Matthew L
ML
Hammond
S Katharine
SK
Glantz
Stanton A
SA
Grossman
William
W
Balmes
John R
JR
Yeghiazarians
Yerem
Y
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
D014028:Tobacco Smoke Pollution; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D003367:Cotinine