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Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis
Open accessAbstract
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.
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“Loss of AXL does not appear to have deleterious effects on embryonic development or normal adult tissue function in mice”
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“…restriction in mice induces venous thrombosis resembling human DVT Most of our current mechanistic knowledge regarding DVT pathophysiology has been gained from mouse models using denudation of the venous endothelial surface (Eitzman et al., 2000; Angelillo-Scherrer et al., 2001; Wang et al., 2006).”
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“Mouse knockouts have also been reported for Gas6 (Angelillo-Scherrer et al., 2001), and it will be of interest to examine circulating levels of inflammatory cytokines in these mutants.”
Background
Metadata
- Authors
- Angelillo-Scherrer, A., de Frutos, P. G., Aparicio, C., Melis, E., Savi, P., Lupu, F., Arnout, J., Dewerchin, M., Hoylaerts, M. F., Herbert, J.-M., Collen, D., Dahlbäck, B., & Carmeliet, P.
- Affiliations
- Lund University (SE)
- Sanofi (France) (FR)
- Thrombosis Research Institute (GB)
- Corresponding author
- Carmeliet, Peter
- Venue
- Nature Medicine
- Published
- 2001-02
- Volume
- 7
- Issue
- 2
- Pages
- 215-221
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2137108685
- Cited by
- 441
- References
- 44
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 7 · 2023: 11 · 2022: 8 · 2021: 8 · 2020: 16 · 2019: 12 · 2018: 19 · 2017: 16 · 2016: 26 · 2015: 26 · 2014: 21 · 2013: 14 · 2012: 22
- FWCI
- 8.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Sanofi
- Stiftelsen för Strategisk Forskning
- Medical Research Council
- Topics
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Keywords
- Gas6, thrombosis, platelet dysfunction, platelet aggregation, hemostasis, thromboembolism, platelet secretion, thromboprophylaxis
- MeSH terms
- Growth Arrest-Specific Protein 6, Animals, Blood Platelets, Cell Line, Disease Models, Animal, Female, Hemostasis, Humans, Male, Phenotype, Platelet Aggregation, Proteins, Receptors, Cell Surface, Recombinant Proteins, Thrombosis, Gene Expression, Mice, Knockout, Intercellular Signaling Peptides and Proteins, Mice
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