Exposure to Ambient Air Fine Particulate Matter Prevents VEGF-Induced Mobilization of Endothelial Progenitor Cells from the Bone Marrow.

AIR pollution; ANALYSIS of variance; ANIMAL experimentation; BONE marrow; CARDIOVASCULAR diseases risk factors; CELL culture; ENDOTHELIUM; FLOW cytometry; MICE; RESEARCH funding; STATISTICS; T-test (Statistics); WESTERN immunoblotting; DATA analysis; ENVIRONMENTAL exposure; VASCULAR endothelial growth factors; PARTICULATE matter; DESCRIPTIVE statistics

Background: Exposure to ambient fine particulate matter air pollution (PM2.5; < 2.5 μm in aerodynamic diameter) induces endothelial dysfunction and increases the risk for cardiovascular disease. Endothelial progenitor cells (EPCs) contribute to postnatal endothelial repair and regeneration. In humans and mice, EPC levels are decreased upon exposure to elevated levels of PM2.5.Objective: We examined the mechanism by which PM2.5 exposure suppresses circulating levels of EPCs.Methods: Mice were exposed to HEPA-filtered air or concentrated ambient fine particulate matter (CAP, 30–100 μg/m3) from downtown Louisville (Kentucky) air, and progenitor cells from peripheral blood or bone marrow were analyzed by flow cytometry or by culture ex vivo.Results: Exposure of the mice to CAP (6 hr/day) for 4–30 days progressively decreased circulating levels of EPCs positive for both Flk‑1 and Sca‑1 (Flk‑1+/Sca‑1+) without affecting stem cells positive for Sca‑1 alone (Sca‑1+). After 9 days of exposure, a 7‑day exposure-free period led to complete recovery of the circulating levels of Flk‑1+/Sca‑1+ cells. CAP exposure decreased circulating levels of EPCs independent of apoptosis while simultaneously increasing Flk‑1+/Sca‑1+ cells in the bone marrow. We observed no change in tissue deposition of these cells. CAP exposure suppressed vascular endothelial growth factor (VEGF)-induced Akt and endothelial nitric oxide synthase (eNOS) phosphorylation in the aorta, and it prevented VEGF/AMD3100-induced mobilization of Flk‑1+/Sca‑1+ cells into the peripheral blood. Treatment with stem cell factor/AMD3100 led to a greater increase in circulating Flk‑1+/Sca‑1+ cells in CAP-exposed mice than in mice breathing filtered air. [ABSTRACT FROM AUTHOR]