Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis
(2001) In Nature Medicine 7(2). p.215-221- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/131345
- author
- organization
- publishing date
- 2001
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Medicine
- volume
- 7
- issue
- 2
- pages
- 215 - 221
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000166756300039
- scopus:0035126319
- ISSN
- 1546-170X
- DOI
- 10.1038/84667
- language
- English
- LU publication?
- yes
- id
- 25ec96d3-0334-48a4-a788-b6802c0d10f7 (old id 131345)
- date added to LUP
- 2016-04-01 15:23:43
- date last changed
- 2025-04-04 14:08:20
@article{25ec96d3-0334-48a4-a788-b6802c0d10f7, 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.}}, author = {{Angelillo-Scherrer, Anne and Garcia de Frutos, Pablo and Aparicio, Cristina and Melis, Els and Savi, Pierre and Lupu, Florea and Arnout, Jef and Dewerchin, Mieke and Hoylaerts, Marc F. and Herbert, Jean-Marc and Collen, Désiré and Dahlbäck, Björn and Carmeliet, Peter}}, issn = {{1546-170X}}, language = {{eng}}, number = {{2}}, pages = {{215--221}}, publisher = {{Nature Publishing Group}}, series = {{Nature Medicine}}, title = {{Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis}}, url = {{https://lup.lub.lu.se/search/files/4382960/624199.pdf}}, doi = {{10.1038/84667}}, volume = {{7}}, year = {{2001}}, }