Exposure to ambient air fine particulate matter prevents VEGF-induced mobilization of endothelial progenitor cells from the bone marrow.
Exposure to ambient air fine particulate matter prevents VEGF-induced mobilization of endothelial progenitor cells from the bone marrow.
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DOI：
10.1289/ehp.1104206
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发表时间：
2012-06
影响因子：
10.4
通讯作者：
Conklin DJ
中科院分区：
文献类型：
--
作者：
Haberzettl P;Lee J;Duggineni D;McCracken J;Bolanowski D;O'Toole TE;Bhatnagar A;Conklin DJ
工作背景：暴露于环境细颗粒物空气污染（PM2.5;空气动力学直径< 2.5 µm）会诱导内皮功能障碍，并增加心血管疾病的风险。内皮祖细胞（EPCs）有助于出生后内皮修复和再生。在人类和小鼠中，EPC水平在暴露于升高的PM2.5水平时降低。目的：我们研究了PM2.5暴露抑制循环EPCs水平的机制。研究方法：将小鼠暴露于HEPA过滤的空气或来自路易斯维尔（肯塔基州）市中心空气的浓缩环境细颗粒物（CAP，30-100 µg/m3），并通过流式细胞术或离体培养分析外周血或骨髓的祖细胞。结果如下：将小鼠暴露于CAP（6小时/天）4-30天逐渐降低了对Flk-1和Sca-1均呈阳性的EPC的循环水平（Flk-1+/Sca-1+），而不影响单独对Sca-1呈阳性的干细胞（Sca-1+）。暴露9天后，7天无暴露期导致Flk-1+/Sca-1+细胞的循环水平完全恢复。CAP暴露降低了不依赖于凋亡的EPCs的循环水平，同时增加了骨髓中的Flk-1+/Sca-1+细胞。我们观察到这些细胞的组织沉积没有变化。CAP暴露抑制了主动脉中血管内皮生长因子（VEGF）诱导的Akt和内皮型一氧化氮合酶（eNOS）磷酸化，并阻止了VEGF/AMD 3100诱导的Flk-1+/Sca-1+细胞动员进入外周血。干细胞因子/AMD 3100处理导致CAP暴露小鼠中循环Flk-1+/Sca-1+细胞的增加大于呼吸过滤空气的小鼠。结论：暴露于PM2.5通过抑制c-kit激活上游的VEGF受体刺激触发的信号传导事件来阻止EPC动员到外周血，从而增加骨髓中的EPC水平。PM2.5对EPC动员的抑制可诱导血管修复或再生的缺陷。
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. Conclusion: Exposure to PM2.5 increases EPC levels in the bone marrow by preventing their mobilization to the peripheral blood via inhibition of signaling events triggered by VEGF-receptor stimulation that are upstream of c-kit activation. Suppression of EPC mobilization by PM2.5 could induce deficits in vascular repair or regeneration.
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DOI：
10.1056/nejmsa0805646
发表时间：
2009-01-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Pope CA 3rd;Ezzati M;Dockery DW
通讯作者：
Dockery DW
影响因子：
16.2
作者：
Fadini, Gian Paolo;Boscaro, Elisa;Avogaro, Angelo
通讯作者：
Avogaro, Angelo
影响因子：
20.1
作者：
Vasa, M;Fichtlscherer, S;Dimmeler, S
通讯作者：
Dimmeler, S
影响因子：
20.1
作者：
Friedrich, EB;Walenta, K;Werner, N
通讯作者：
Werner, N
影响因子：
4.9
作者：
Brook, Robert D.;Bard, Robert L.;Williams, Ron
通讯作者：
Williams, Ron