Universität zu Köln

Utermoehlen, Olaf, Jakobshagen, Kristin, Blissenbach, Birgit, Wiegmann, Katja, Merz, Tobias, Hefti, Jacqueline Pichler and Kroenke, Martin (2019). Emergence of AnnexinV(pos) CD31(neg) CD42b(low/neg) extracellular vesicles in plasma of humans at extreme altitude. PLoS One, 14 (8). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Background 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 hypoxiainduced vascular dysfunction. Methods and findings 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 AnnexinV(pos), 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 CD31(pos) CD42(neg) EEV as well as of CD31(pos) CD42b(pos) PEV at the same time giving rise to a quantitatively prevailing CD31(neg) CD42b(low/neg) subpopulation of AnnexinV(pos) EV. An almost hundredfold increase in the numbers of this previously unrecognized population of CD31 neg CD42b(low/neg) EV was observed in all participants reaching 7,050m asl. Conclusions The emergence of CD31(neg) CD42b(low/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 AnnexinV(pos) EV subpopulations may serve as early and sensitive indicators of compromised vascular homeostasis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Utermoehlen, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Jakobshagen, Kristin UNSPECIFIED UNSPECIFIED UNSPECIFIED Blissenbach, Birgit UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiegmann, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Merz, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Hefti, Jacqueline Pichler UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroenke, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-145178
DOI:	10.1371/journal.pone.0220133
Journal or Publication Title:	PLoS One
Volume:	14
Number:	8
Date:	2019
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TUMOR-NECROSIS-FACTOR; VE-CADHERIN; ENDOTHELIAL MICROPARTICLES; ADHESION MOLECULE-1; OXIDATIVE STRESS; PLATELETS; ADHERENCE; JUNCTIONS; DISTINCT; RELEASE Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14517