Brewster, L. Madden, Anthony R. Bain, Vinicius P. Garcia, Noah M. DeSouza, Michael M. Tymko, Jared J. Greiner, and Philip N. Ainslie. Global REACH 2018: high altitude-related circulating extracellular microvesicles promote a proinflammatory endothelial phenotype in vitro. High Alt Med Biol. 24:223-229, 2023. Introduction: Ascent to high altitude (HA) can induce vascular dysfunction by promoting a proinflammatory endothelial phenotype. Circulating microvesicles (MVs) can mediate the vascular endothelium and inflammation. It is unclear whether HA-related MVs are associated with endothelial inflammation. Objectives: We tested the hypothesis that MVs derived from ascent to HA induce a proinflammatory endothelial phenotype. Methods: Ten healthy adults (8 M/2 F; age: 28 ± 2 years) residing at sea level (SL) were studied before and 4-6 days after rapid ascent to HA (4,300 m). MVs were isolated and enumerated from plasma by centrifugation and flow cytometry. Human umbilical vein endothelial cells were treated with MVs collected from each subject at SL (MV-SL) and at HA (MV-HA). Results: Circulating MV number significantly increased at HA (26,637 ± 3,315 vs. 19,388 ± 1,699). Although intracellular expression of total nuclear factor kappa beta (NF-κB; 83.4 ± 6.7 arbitrary units [AU] vs. 90.2 ± 6.9 AU) was not affected, MV-HA resulted in ∼55% higher (p < 0.05) active NF-κB (129.6 ± 19.8 AU vs. 90.7 ± 10.5 AU) expression compared with MV-SL. In addition, MV-HA induced higher interleukin (IL)-6 (63.9 ± 3.9 pg/ml vs. 53.3 ± 3.6 pg/ml) and IL-8 (140.2 ± 3.6 pg/ml vs. 120.7 ± 3.8 pg/ml) release compared with MV-SL, which was blunted with NF-κB blockade. Conclusions: Circulating extracellular MVs increase at HA and induce endothelial inflammation, potentially contributing to altitude-related vascular dysfunction.

中文翻译：

---

Global REACH 2018：高海拔相关循环细胞外微泡在体外促进促炎内皮表型。

布鲁斯特、L. Madden、安东尼 R. 贝恩、Vinicius P. Garcia、Noah M. DeSouza、Michael M. Tymko、Jared J. Greiner 和 Philip N. Ainslie。Global REACH 2018：高海拔相关的循环细胞外微泡在体外促进促炎内皮表型。高替代医学生物。24:223-229, 2023。简介：上升到高海拔 (HA) 可以通过促进促炎内皮表型来诱导血管功能障碍。循环微泡（MV）可以介导血管内皮和炎症。目前尚不清楚 HA 相关的 MV 是否与内皮炎症有关。目的：我们测试了以下假设：上升至 HA 所产生的 MV 会诱导促炎内皮表型。方法：对居住在海平面 (SL) 的 10 名健康成年人（8 M/2 F；年龄：28 ± 2 岁）在快速攀登至 HA (4,300 m) 之前和之后 4-6 天进行了研究。通过离心和流式细胞术从血浆中分离并计数MV。在 SL (MV-SL) 和 HA (MV-HA) 时用从每个受试者收集的 MV 处理人脐静脉内皮细胞。结果：HA 时循环 MV 数量显着增加（26,637 ± 3,315 vs. 19,388 ± 1,699）。尽管总核因子 kappa beta（NF-κB；83.4 ± 6.7 任意单位 [AU] 与 90.2 ± 6.9 AU）的细胞内表达未受影响，但 MV-HA 导致活性 NF- 增加约 55%（p < 0.05）。与 MV-SL 相比，κB（129.6 ± 19.8 AU vs. 90.7 ± 10.5 AU）表达。此外，MV-HA 诱导较高的白细胞介素 (IL)-6（63.9 ± 3.9 pg/ml 对比 53.3 ± 3.6 pg/ml）和 IL-8（140.2 ± 3.6 pg/ml 对比 120.7 ± 3.8 pg/ml）与 MV-SL 相比，MV-SL 的释放量因 NF-κB 阻断而减弱。结论：HA 时循环细胞外 MV 增加并诱发内皮炎症，可能导致与海拔相关的血管功能障碍。