Hypoxia impairs agonist-induced integrin αIIbβ3 activation and platelet aggregation

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 affec...

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Autores principales:	Klytaimnistra Kiouptsi, Stepan Gambaryan, Elena Walter, Ulrich Walter, Kerstin Jurk, Christoph Reinhardt
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a758cf7e3e61420a87ab6cf63bc5d18d
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spelling	oai:doaj.org-article:a758cf7e3e61420a87ab6cf63bc5d18d2021-12-02T11:51:02ZHypoxia impairs agonist-induced integrin αIIbβ3 activation and platelet aggregation10.1038/s41598-017-07988-x2045-2322https://doaj.org/article/a758cf7e3e61420a87ab6cf63bc5d18d2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07988-xhttps://doaj.org/toc/2045-2322Abstract 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.Klytaimnistra KiouptsiStepan GambaryanElena WalterUlrich WalterKerstin JurkChristoph ReinhardtNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Klytaimnistra Kiouptsi Stepan Gambaryan Elena Walter Ulrich Walter Kerstin Jurk Christoph Reinhardt Hypoxia impairs agonist-induced integrin αIIbβ3 activation and platelet aggregation
description	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.
format	article
author	Klytaimnistra Kiouptsi Stepan Gambaryan Elena Walter Ulrich Walter Kerstin Jurk Christoph Reinhardt
author_facet	Klytaimnistra Kiouptsi Stepan Gambaryan Elena Walter Ulrich Walter Kerstin Jurk Christoph Reinhardt
author_sort	Klytaimnistra Kiouptsi
title	Hypoxia impairs agonist-induced integrin αIIbβ3 activation and platelet aggregation
title_short	Hypoxia impairs agonist-induced integrin αIIbβ3 activation and platelet aggregation
title_full	Hypoxia impairs agonist-induced integrin αIIbβ3 activation and platelet aggregation
title_fullStr	Hypoxia impairs agonist-induced integrin αIIbβ3 activation and platelet aggregation
title_full_unstemmed	Hypoxia impairs agonist-induced integrin αIIbβ3 activation and platelet aggregation
title_sort	hypoxia impairs agonist-induced integrin αiibβ3 activation and platelet aggregation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a758cf7e3e61420a87ab6cf63bc5d18d
work_keys_str_mv	AT klytaimnistrakiouptsi hypoxiaimpairsagonistinducedintegrinaiibb3activationandplateletaggregation AT stepangambaryan hypoxiaimpairsagonistinducedintegrinaiibb3activationandplateletaggregation AT elenawalter hypoxiaimpairsagonistinducedintegrinaiibb3activationandplateletaggregation AT ulrichwalter hypoxiaimpairsagonistinducedintegrinaiibb3activationandplateletaggregation AT kerstinjurk hypoxiaimpairsagonistinducedintegrinaiibb3activationandplateletaggregation AT christophreinhardt hypoxiaimpairsagonistinducedintegrinaiibb3activationandplateletaggregation
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Hypoxia impairs agonist-induced integrin αIIbβ3 activation and platelet aggregation

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