Authors:	Kiouptsi, Klytaimnistra Gambaryan, Stepan Walter, Elena Walter, Ulrich Jurk, Kerstin Reinhardt, Christoph
Title:	Hypoxia impairs agonist-induced integrin αIIbβ3 activation and platelet aggregation
Online publication date:	14-Jul-2022
Year of first publication:	2017
Language:	english
Abstract:	Under ischemic conditions, tissues are exposed to hypoxia. Although human physiology, to a certain extent, can adapt to hypoxic conditions, the impact of low oxygen levels on platelet function is unresolved. Therefore, we explored how reduction of atmospheric oxygen levels to 1% might affect agonist-induced aggregation and static adhesion of isolated human platelets. We uncovered that isolated, washed human platelets exposed to hypoxic conditions show reduced thrombin receptor-activating peptide-6 (TRAP-6) and convulxin-induced aggregation. Of note, this hypoxia-triggered effect was not observed in platelet-rich plasma. Independent of the agonist used (TRAP-6, ADP), activation of the platelet fibrinogen receptor integrin αIIbβ3 (GPIIbIIIa, CD41/CD61) was strongly reduced at 1% and 8% oxygen. The difference in agonist-induced integrin αIIbβ3 activation was apparent within 5 minutes of stimulation. Following hypoxia, re-oxygenation resulted in the recovery of integrin αIIbβ3 activation. Importantly, platelet secretion was not impaired by hypoxia. Static adhesion experiments revealed decreased platelet deposition to fibrinogen coatings, but not to collagen or vitronectin coatings, indicating that specifically the function of the integrin subunit αIIb is impaired by exposure of platelets to reduced oxygen levels. Our results reveal an unexpected effect of oxygen deprivation on platelet aggregation mediated by the fibrinogen receptor integrin αIIbβ3.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7417
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Scientific reports 7
Pages or article number:	Art. 7621
Publisher:	Macmillan Publishers Limited, part of Springer Nature
Publisher place:	London
Issue date:	2017
ISSN:	2045-2322
Publisher URL:	http://dx.doi.org/10.1038/s41598-017-07988-x
Publisher DOI:	10.1038/s41598-017-07988-x
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)