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

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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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

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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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