The Effects of Concentrated Ambient Particles (CAPs) on Endothelial Progenitor Cell Number

ERIC NICHOLAS LIBERDA (1), AJ Madrid (1), Qingshan Qu (1), Lung Chi Chen (1)

(1) New York University, New York City, NY

     Abstract Number: 193
     Last modified: November 8, 2009

Abstract
Introduction: Particulate matter has been associated with an increased risk of mortality in human population studies and significant increases in vascular inflammation, generation of reactive oxygen species (ROS), altered vasomotor tone, and potentiated atherosclerosis in murine exposures. Endothelial progenitor cells (EPCs), endogenous semi-pluripotent stem cells that aid in endothelial repair, are decreased in count and impaired in function for various chronic disease states. Given the truly important role that EPCs play in the maintenance and repair of the cardiovascular endothelium, it is very likely that perturbations to the EPC system from chronic inflammatory and oxidative stress assaults by CAPs cause adverse effects in the cardiovascular endothelium. Furthermore, due to the ubiquity of air pollution from countless anthropogenic sources combined with evidence from cardiovascular epidemiological and toxicological studies, research into the mechanisms that drive the resultant cardiovascular disease states is quickly becoming a pressing issue. Thus, to determine if concentrated ambient particles (CAPs) can adversely affect the count of EPCs, various inhalation exposures were performed.

Methods: In order to evaluate the effects of air pollutants on EPCs, mice were exposed to either filtered air (control) or CAPs using the versatile aerosol concentration enrichment system (VACES) developed by Sioutas et al. (1999) and modified by our group (Maciejczyk et al. 2005) for use in animal model exposures at the Department of Environmental Medicine, NYU School of Medicine. Several CAPs exposures were performed such that EPC counts could be performed using flow cytometry from lysed blood, bone marrow, or both, in ApoE -/- and C57BL/6 mice. EPCs were assessed using CD-34+/VEGF-R2+/CD-11b- and more recently, SCA-1+/VEGF-R2+/CD-45- antigens on a Becton Dickinson FACScalibur system (Fluorescence-activated cell sorter flow cytometer) equipped with a 15 mW argon laser (488 nm) and a 17 mW HeNe laser (633 nm), as well as cultured for 7 days and stained for acLDL uptake and CD-31 or GS-lectin.

Results and Conclusions: Significant differences between exposure and control groups for long term CAPs exposures and were observed. It appears that EPCs in bone marrow initially decrease, then rebound during the acute phase of the exposure (up to 4 months), and ultimately become depleted after sustained injury (6 months). EPCs in lysed blood remain constantly depressed over controls indicating that they may be quickly recruited from the circulation to sites of injury. In conclusion, this study shows that chronic inhalation of CAPs results in depressed EPCs in both bone marrow and lysed blood.