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dc.contributor.authorWen, Laien_US
dc.contributor.authorFeil, Susanneen_US
dc.contributor.authorWolters, Markusen_US
dc.contributor.authorThunemann, Martinen_US
dc.contributor.authorRegler, Franken_US
dc.contributor.authorSchmidt, Kjestineen_US
dc.contributor.authorFriebe, Andreasen_US
dc.contributor.authorOlbrich, Marcusen_US
dc.contributor.authorLanger, Haralden_US
dc.contributor.authorGawaz, Meinraden_US
dc.contributor.authorde Wit, Coren_US
dc.contributor.authorFeil, Roberten_US
dc.coverage.spatialEnglanden_US
dc.date2018-09-18
dc.date.accessioned2020-12-18T15:06:42Z
dc.date.available2020-12-18T15:06:42Z
dc.date.issued2018-10-16
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30327468
dc.identifier.citationLai Wen, Susanne Feil, Markus Wolters, Martin Thunemann, Frank Regler, Kjestine Schmidt, Andreas Friebe, Marcus Olbrich, Harald Langer, Meinrad Gawaz, Cor de Wit, Robert Feil. 2018. "A shear-dependent NO-cGMP-cGKI cascade in platelets acts as an auto-regulatory brake of thrombosis.." Nat Commun, Volume 9, Issue 1, pp. 4301 - ?. https://doi.org/10.1038/s41467-018-06638-8
dc.identifier.issn2041-1723
dc.identifier.urihttps://hdl.handle.net/2144/41824
dc.description.abstractMechanisms that limit thrombosis are poorly defined. One of the few known endogenous platelet inhibitors is nitric oxide (NO). NO activates NO sensitive guanylyl cyclase (NO-GC) in platelets, resulting in an increase of cyclic guanosine monophosphate (cGMP). Here we show, using cGMP sensor mice to study spatiotemporal dynamics of platelet cGMP, that NO-induced cGMP production in pre-activated platelets is strongly shear-dependent. We delineate a new mode of platelet-inhibitory mechanotransduction via shear-activated NO-GC followed by cGMP synthesis, activation of cGMP-dependent protein kinase I (cGKI), and suppression of Ca2+ signaling. Correlative profiling of cGMP dynamics and thrombus formation in vivo indicates that high cGMP concentrations in shear-exposed platelets at the thrombus periphery limit thrombosis, primarily through facilitation of thrombus dissolution. We propose that an increase in shear stress during thrombus growth activates the NO-cGMP-cGKI pathway, which acts as an auto-regulatory brake to prevent vessel occlusion, while preserving wound closure under low shear.en_US
dc.description.sponsorshipFE 438/5-1 - Deutsche Forschungsgemeinschaft (German Research Foundation); FE 438/6-1 - Deutsche Forschungsgemeinschaft (German Research Foundation); FE 438/7-1 - Deutsche Forschungsgemeinschaft (German Research Foundation); FE 438/8-2 - Deutsche Forschungsgemeinschaft (German Research Foundation)en_US
dc.format.extentp. 4301en_US
dc.languageeng
dc.language.isoen_US
dc.relation.ispartofNat Commun
dc.rights© The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAnimalsen_US
dc.subjectBlood plateletsen_US
dc.subjectCalciumen_US
dc.subjectCyclic GMPen_US
dc.subjectCyclic GMP-dependent protein kinase type Ien_US
dc.subjectFluorescence resonance energy transferen_US
dc.subjectHumansen_US
dc.subjectMice, transgenicen_US
dc.subjectNitric oxideen_US
dc.subjectPlatelet activationen_US
dc.subjectSignal transductionen_US
dc.subjectStress, mechanicalen_US
dc.subjectThrombosisen_US
dc.titleA shear-dependent NO-cGMP-cGKI cascade in platelets acts as an auto-regulatory brake of thrombosisen_US
dc.typeArticleen_US
dc.description.versionPublished versionen_US
dc.identifier.doi10.1038/s41467-018-06638-8
pubs.elements-sourcepubmeden_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Engineeringen_US
pubs.publication-statusPublished onlineen_US
dc.identifier.orcid0000-0003-4139-079X (Thunemann, Martin)
dc.identifier.mycv575732


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© The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as © The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/