Author + information
- Received October 10, 2007
- Revision received December 12, 2007
- Accepted January 14, 2008
- Published online May 6, 2008.
- 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⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Yerem Yeghiazarians, University of California, San Francisco, 505 Parnassus Avenue, L-523, Box 0103, San Francisco, California 94143-0103.
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.
This work was supported by awards from the Flight Attendant Medical Research Institute to Dr. Lee, the American Heart Association to Drs. Heiss and Springer, the Wayne and Gladys Valley Foundation to Dr. Grossman, and the UCSF Cardiac Stem Cell Foundation to Dr. Yeghiazarians. The funding agencies played no role in the conduct of the research or preparation of the article. Drs. Heiss and Amabile contributed equally to this work. Dr. Heiss is currently affiliated with the University RWTH Aachen, Medizinische Klinik 1, Aachen, Germany.
- Received October 10, 2007.
- Revision received December 12, 2007.
- Accepted January 14, 2008.
- American College of Cardiology Foundation