CLINICAL RESEARCH: VASCULAR DISORDER
Brief Secondhand Smoke Exposure Depresses Endothelial Progenitor Cells Activity and Endothelial FunctionSustained Vascular Injury and Blunted Nitric Oxide Production
Christian Heiss, MD, Dr Med*,
Nicolas Amabile, MD*,
Andrew C. Lee, MD*,
Wendy May Real, BS*,
Suzaynn F. Schick, PhD ,
David Lao, MD*,
Maelene L. Wong, BS*,
Sarah Jahn, MB*,
Franca S. Angeli, MD*,
Petros Minasi, BA*,
Matthew L. Springer, PhD*,
S. Katharine Hammond, PhD ,
Stanton A. Glantz, PhD, FACC*,
William Grossman, MD, FACC*,
John R. Balmes, MD*, and
Yerem Yeghiazarians, MD, FACC*,*
* Division of Cardiology, Department of Medicine, University of California, San Francisco, California
Division of Occupational and Environmental Medicine, Department of Medicine, University of California, San Francisco, California
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, California.
Manuscript received October 10, 2007;
revised manuscript received December 12, 2007,
accepted January 14, 2008.
* Reprint requests and correspondence: Dr. Yerem Yeghiazarians, University of California, San Francisco, 505 Parnassus Avenue, L-523, Box 0103, San Francisco, California 94143-0103. (Email: yeghiaza{at}medicine.ucsf.edu).
Objectives: 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.
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Abbreviations and Acronyms
| | BrdU = bromodeoxyuridine | | BSA = bovine serum albumin | | DAF = diaminofluorescein | | EMP = endothelial microparticle | | EPC = endothelial progenitor cell | | FMD = flow-mediated dilation | | L-NMMA = LG-monomethyl-arginine | | NO = nitric oxide | | PE = phycoerythrin | | SHS = secondhand smoke | | UEA = Ulex europeus agglutinin | | VEGF = vascular endothelial growth factor |
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