Episodic exposure to fine particulate air pollution decreases circulating levels of endothelial progenitor cells

Abstract

Rationale: Acute and chronic exposures to airborne particulate matter (PM) have been linked in epidemiological studies to a wide spectrum of cardiovascular disorders that are characterized by a dysfunctional endothelium. The pathophysiological mechanisms underlying these associations are unclear.

Objective: To examine whether exposure to fine PM with an aerodynamic diameter of <2.5 microm (PM(2.5)) affects the circulating levels of endothelial progenitor cell (EPC) populations, systemic inflammation and coagulation.

Methods and results: Phenotypically distinct EPC populations were quantified by flow cytometry in young (18 to 25 years) adult humans exposed to episodic increases in PM(2.5) along the Wasatch Mountain Front in Utah. In addition, Sca-1+/Flk-1+ cells were measured in the peripheral blood of mice exposed to concentrated particles from ambient air in Louisville, Ky. In both studies, PM exposure was negatively correlated with circulating EPC levels. In humans, statistically significant associations between PM(2.5) exposure and the plasma levels of platelet-monocyte aggregates, high-density lipoprotein, and nonalbumin protein were also observed. Episodic increases in PM(2.5) did not change plasma levels of C-reactive protein, interleukin-1beta, interleukin-6, fibrinogen, or serum amyloid A.

Conclusions: Episodic exposure to PM(2.5) induces reversible vascular injury, reflected in part by depletion of circulating EPC levels, and increases in platelet activation and the plasma level of high-density lipoprotein. These changes were also accompanied by an increase in nonalbumin protein and may be related to mechanisms by which exposure to particulate air pollution increases the risk of cardiovascular disease and adverse cardiovascular events.

Figures

Figure 1. PM2.5 levels are inversely correlated with human EPC number

(A) Twelve h lagged moving average PM2.5 levels (solid and dashed black lines) and the daily 24-hr PM2.5 concentrations (blue and green lines) recorded at two monitoring sites in the Utah Valley between January 1-March 5, 2009. Red dots represent the times of blood draws; (B) Regression analysis of the relationship between CD31+/CD34+/CD45+/CD133+ cells (normalized to volume) and previous 24-h PM2.5 level; and (C) regression analysis of the relationship between non-albumin protein (as a percent of total plasma protein) and average previous 24-h PM2.5 levels. Individual data points are labeled with the subject numbers and individual-level regression is represented by dotted lines. Solid line represents regression analysis from the pooled fixed-effects regression model.

Figure 2. PM exposure decreases EPC levels in mice

Flow cytometric analysis of peripheral blood obtained from mice exposed to filtered air or concentrated air particulates. (A) Sca-1+/Flk-1+ cells (right panels) were quantified in a gated lymphocyte population identified in an SSC vs. FSC dot plot (left panels). (B) EPC levels per μl blood in mice exposed to air or PM2.5 during the indicated exposure periods (n=4, July 2009, n=8, May 2010; * p<0.05).