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Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis

Angelillo-Scherrer, Anne; Garcia de Frutos, Pablo LU ; Aparicio, Cristina; Melis, Els; Savi, Pierre; Lupu, Florea; Arnout, Jef; Dewerchin, Mieke; Hoylaerts, Marc F. and Herbert, Jean-Marc, et al. (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)
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publication status
published
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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
2007-07-24 10:48:36
date last changed
2018-07-29 03:52:36
@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          = {http://dx.doi.org/10.1038/84667},
  volume       = {7},
  year         = {2001},
}