Institute for Medical Microbiology, Immunology and Hygiene, University Hospital Cologne, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), Cologne, Germany.
PLoS One. 2019 Aug 1;14(8):e0220133. doi: 10.1371/journal.pone.0220133. eCollection 2019.
Hypobaric hypoxia has been reported to cause endothelial cell and platelet dysfunction implicated in the formation of microvascular lesions, and in its extremes may contribute to vascular leakage in high altitude pulmonary edema or blood brain barrier disruption leading to cerebral micro-hemorrhage (MH). Platelet function in the development of microvascular lesions remained ill defined, and is still incompletely understood. In this study platelet- and endothelial cell-derived extracellular vesicles (PEV and EEV, respectively) and cell adhesion molecules were characterized in plasma samples of members of a high altitude expedition to delineate the contribution of platelets and endothelial cells to hypobaric hypoxia-induced vascular dysfunction.
In this observational study, platelet and endothelial cell-derived extracellular vesicles were analysed by flow-cytometry in plasma samples from 39 mountaineers participating in a medical research climbing expedition to Himlung Himal, Nepal, 7,050m asl. Megakaryocyte/platelet-derived AnnexinVpos, PECAM-1 (CD31) and glycoprotein-1b (GP1b, CD42b) positive extracellular vesicles (PEV) constituted the predominant fraction of EV in plasma samples up to 6,050m asl. Exposure to an altitude of 7,050m led to a marked decline of CD31pos CD42neg EEV as well as of CD31pos CD42bpos PEV at the same time giving rise to a quantitatively prevailing CD31neg CD42blow/neg subpopulation of AnnexinVpos EV. An almost hundredfold increase in the numbers of this previously unrecognized population of CD31neg CD42blow/neg EV was observed in all participants reaching 7,050m asl.
The emergence of CD31neg CD42blow/neg EV was observed in all participants and thus represents an early hypoxic marker at extreme altitude. Since CD31 and CD42b are required for platelet-endothelial cell interactions, these hypobaric hypoxia-dependent quantitative and phenotypic changes of AnnexinVpos EV subpopulations may serve as early and sensitive indicators of compromised vascular homeostasis.
低气压缺氧已被报道可导致内皮细胞和血小板功能障碍，从而形成微血管病变，在极端情况下，可能导致高原性肺水肿中的血管渗漏或血脑屏障破坏导致脑微出血 (MH)。血小板在微血管病变发展中的作用仍不明确，目前仍不完全清楚。在这项研究中，我们分别对高海拔探险队成员的血浆样本中的血小板和内皮细胞衍生的细胞外囊泡 (PEV 和 EEV) 和细胞黏附分子进行了特征描述，以阐明血小板和内皮细胞对低气压缺氧诱导的血管功能障碍的贡献。
在这项观察性研究中，我们通过流式细胞术分析了来自 39 名参与尼泊尔 Himlung Himal 医学研究登山探险队的登山者的血浆样本中的血小板和内皮细胞衍生的细胞外囊泡。巨核细胞/血小板衍生的 AnnexinVpos、PECAM-1 (CD31) 和糖蛋白-1b (CD42b) 阳性细胞外囊泡 (PEV) 在 6050m 海拔以下的血浆样本中构成了 EV 的主要部分。暴露于 7050m 海拔高度会导致 CD31pos CD42neg EEV 的显著下降，同时也会导致 CD31pos CD42bpos PEV 的下降，同时产生定量上占主导地位的 AnnexinVpos EV 的 CD31neg CD42blow/neg 亚群。在所有达到 7050m 海拔高度的参与者中，观察到这种以前未被识别的 CD31neg CD42blow/neg EV 数量增加了近百倍。
在所有参与者中均观察到 CD31neg CD42blow/neg EV 的出现，因此代表了极端海拔高度下的早期缺氧标志物。由于 CD31 和 CD42b 是血小板-内皮细胞相互作用所必需的，因此 AnnexinVpos EV 亚群的这种低气压缺氧依赖性数量和表型变化可能作为血管稳态受损的早期和敏感指标。
