Deficiency or inhibition of gas6 causes platelet dysfunction and protects mice against thrombosis

Deficiency or inhibition of gas6 causes platelet dysfunction and protects mice against thrombosis


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ABSTRACT The growth arrest-specific gene 6 product (Gas6) is a secreted protein related to the anticoagulant protein S but its role in hemostasis is unknown. Here we show that inactivation


of the _Gas6_ gene prevented venous and arterial thrombosis in mice, and protected against fatal collagen/epinephrine-induced thrombo embolism. _Gas6_−/− mice did not, however, suffer


spontaneous bleeding and had normal bleeding after tail clipping. In addition, we found that Gas6 antibodies inhibited platelet aggregation _in vitro_ and protected mice against fatal


thrombo embolism without causing bleeding _in vivo_. Gas6 amplified platelet aggregation and secretion in response to known agonists. Platelet dysfunction in _Gas6_−/− mice resembled that of


patients with platelet signaling transduction defects. Thus, Gas6 is a platelet-response amplifier that plays a significant role in thrombosis. These findings warrant further evaluation of


the possible therapeutic use of Gas6 inhibition for prevention of thrombosis. Access through your institution Buy or subscribe This is a preview of subscription content, access via your


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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS ACKR3 REGULATES PLATELET ACTIVATION AND ISCHEMIA-REPERFUSION


TISSUE INJURY Article Open access 05 April 2022 PLATELET GLYCOPROTEIN V SPATIO-TEMPORALLY CONTROLS FIBRIN FORMATION Article Open access 23 March 2023 LOSS OF SOLUBLE GUANYLYL CYCLASE IN


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Download references ACKNOWLEDGEMENTS We thank K. Bijnens, A. Bouché, I. Cartois, E. Demarsin, M. De Mol, K. Deroover, E. Gils, B. Hermans, S. Jansen, L. Kieckens, T. Vancoetsem, A.


Vandenhoeck, I. Vanlinthout, M. Vanrusselt, P. Vanwesemael, I. Vreys and S. Wyns for technical assistance and J. Vermylen for critical reading of the manuscript. This work was supported by


Sanofi Research and the Swedish Medical Research Council (Grants 07143, 12561 and 13000) and a Senior Investigators Award from the Swedish Foundation for Strategic Research. A.


Angelillo-Scherrer is a recipient of awards from the Swiss National Foundation for Scientific Research and the Fondation Suisse pour les Bourses en Médecine et Biologie. AUTHOR INFORMATION


Author notes * Anne Angelillo-Scherrer and Pablo Garcia de Frutos: A.A.S. and P.G.F. contributed equally to this study. AUTHORS AND AFFILIATIONS * The Center for Transgene Technology and


Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium Anne Angelillo-Scherrer, Els Melis, Jef Arnout, Mieke Dewerchin, Marc F. Hoylaerts, Désiré Collen & 


Peter Carmeliet * Department of Clinical Chemistry, Lund University, Wallenberg Laboratory, Malmö University Hospital, Malmö, Sweden Pablo Garcia de Frutos, Cristina Aparicio & Björn


Dahlbäck * Cardiovascular/Thrombosis Research Department, Sanofi∼Synthélabo, Toulouse, France Pierre Savi & Jean-Marc Herbert * Thrombosis Research Institute, Vascular Biology


Laboratory, London, UK Florea Lupu Authors * Anne Angelillo-Scherrer View author publications You can also search for this author inPubMed Google Scholar * Pablo Garcia de Frutos View author


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Scholar * Mieke Dewerchin View author publications You can also search for this author inPubMed Google Scholar * Marc F. Hoylaerts View author publications You can also search for this


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ARTICLE CITE THIS ARTICLE Angelillo-Scherrer, A., de Frutos, P., Aparicio, C. _et al._ Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. _Nat


Med_ 7, 215–221 (2001). https://doi.org/10.1038/84667 Download citation * Received: 19 September 2000 * Accepted: 15 December 2000 * Issue Date: February 2001 * DOI:


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