From the Department of Medicine, Diabetes and Obesity Center, Institute of Molecular Cardiology, University of Louisville, KY.
Arterioscler Thromb Vasc Biol. 2018 Jan;38(1):131-142. doi: 10.1161/ATVBAHA.117.309971. Epub 2017 Nov 30.
Exposure to fine particulate matter (PM) air pollution is associated with the depletion of circulating endothelial progenitor cells (EPCs), as well as vascular injury and dysfunction. Nevertheless, it remains unclear whether PM exposure leads to significant impairments in EPC function. Hence, we studied the effects of PM on EPC-mediated recovery of vascular perfusion after hindlimb ischemia and examined the mechanisms whereby PM exposure affects EPC abundance and function.
In comparison with EPCs isolated from mice breathing filtered air, EPCs from mice exposed for 9 consecutive days (6 hours per day) to concentrated ambient PM (CAP) had defects in both proliferation and tube formation. However, CAP exposure of mice overexpressing extracellular superoxide dismutase (ecSOD-Tg) in the lungs did not affect EPC tube formation. Exposure to CAP also suppressed circulating EPC levels, VEGF (vascular endothelial growth factor)-stimulated aortic Akt phosphorylation, and plasma NO levels in wild-type but not in ecSOD-Tg mice. EPCs from CAP-exposed wild-type mice failed to augment basal recovery of hindlimb perfusion when injected into unexposed mice subjected to hindlimb ischemia; however, these deficits in recovery of hindlimb perfusion were absent when using EPCs derived from CAP-exposed ecSOD-Tg mice. The improved reparative function of EPCs from CAP-exposed ecSOD-Tg mice was also reflected by greater expression of and when compared with EPCs from CAP-exposed wild-type mice.
Exposure to PM impairs EPC abundance and function and prevents EPC-mediated vascular recovery after hindlimb ischemia. This defect is attributed, in part, to pulmonary oxidative stress and was associated with vascular VEGF resistance and a decrement in NO bioavailability.
细颗粒物（PM）空气污染暴露与循环内皮祖细胞（EPC）耗竭以及血管损伤和功能障碍有关。然而，目前尚不清楚 PM 暴露是否会导致 EPC 功能显著受损。因此，我们研究了 PM 对后肢缺血后 EPC 介导的血管灌注恢复的影响，并探讨了 PM 暴露影响 EPC 丰度和功能的机制。
与从呼吸过滤空气的小鼠中分离的 EPC 相比，从连续 9 天（每天 6 小时）暴露于浓缩环境 PM（CAP）的小鼠中分离的 EPC 在增殖和管形成方面均存在缺陷。然而，CAP 暴露于肺部过表达细胞外超氧化物歧化酶（ecSOD-Tg）的小鼠并不影响 EPC 管形成。CAP 暴露还抑制了野生型小鼠的循环 EPC 水平、血管内皮生长因子（VEGF）刺激的主动脉 Akt 磷酸化和血浆 NO 水平，但在 ecSOD-Tg 小鼠中则没有。当注射到未暴露于 CAP 的后肢缺血小鼠中时，来自 CAP 暴露的野生型小鼠的 EPC 未能增强后肢灌注的基础恢复；然而，当使用来自 CAP 暴露的 ecSOD-Tg 小鼠的 EPC 时，后肢灌注恢复的这些缺陷不存在。与来自 CAP 暴露的野生型小鼠的 EPC 相比，来自 CAP 暴露的 ecSOD-Tg 小鼠的 EPC 表达更高，这也反映了 EPC 修复功能的改善。
暴露于 PM 会损害 EPC 的丰度和功能，并防止后肢缺血后 EPC 介导的血管恢复。这种缺陷部分归因于肺氧化应激，并与血管 VEGF 抵抗和 NO 生物利用度降低有关。
