Brief Ultrarapid Communication Episodic Exposure to Fine Particulate Air Pollution Decreases Circulating Levels of Endothelial Progenitor Cells

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. /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-1␤, 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 cardiovas-cular events. A cute and chronic exposure to elevated levels of fine airborne particulate matter (PM) is associated with an increase in the incidence of adverse cardiovascular events, 1,2 atherogenesis, cardio-vascular disease (CVD) risk, and cardiovascular mortality. In urban environments, fine PM (PM with aerodynamic diameter of Ͻ2.5 ␮m [PM 2.5 ]) is generated mostly by fossil fuel combustion in automobiles or by industrial processes. Although several mechanisms have been proposed to account for the link between PM exposure and CVD risk, endothelial dysfunction has emerged as a key feature of PM toxicity. Inhalation of concentrated PM 2.5 induces acute conduit artery vasoconstriction in humans and chronic deficits in endothelium-mediated vasodilation in mice. 1,2 The adult endothelium is a differentiated cell layer that provides a nonthrombotic interface between parenchymal cells and peripheral blood. Defects in its function arise because of the upregulated expression of proinflammatory and prothrombotic molecules or from defective, endogenous repair capacity. Evidence from multiple studies suggests that the endothelium is continually repaired by progenitor cells mobilized from specific niches such as the bone marrow. These cells express both endothelial and stem cell markers, and their circulating levels in blood are reflective of CVD risk and burden. 3,4 The present study was designed to examine how exposure to PM 2.5 affects endothelial progenitor cell (EPC) populations and whether this was …