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Vascular Gas6 contributes to thrombogenesis and promotes tissue factor up-regulation after vessel injury in mice.
- Source :
-
Blood [Blood] 2013 Jan 24; Vol. 121 (4), pp. 692-9. Date of Electronic Publication: 2012 Nov 13. - Publication Year :
- 2013
-
Abstract
- Gas6 (growth-arrest specific gene 6) plays a role in thrombus stabilization. Gas6 null (-/-) mice are protected from lethal venous and arterial thromboembolism through platelet signaling defects induced only by 5 μM ADP and 10 μM of the thromboxane analog, U46619. This subtle platelet defect, despite a dramatic clinical phenotype, raises the possibility that Gas6 from a source other than platelets contributes to thrombus formation. Thus, we hypothesize that Gas6 derived from the vascular wall plays a role in venous thrombus formation. Bone marrow transplantation and platelet depletion/reconstitution experiments generating mice with selective ablations of Gas6 from either the hematopoietic or nonhematopoietic compartments demonstrate an approximately equal contribution by Gas6 from both compartments to thrombus formation. Tissue factor expression was significantly reduced in the vascular wall of Gas6(-/-) mice compared with WT. In vitro, thrombin-induced tissue factor expression was reduced in Gas6(-/-) endothelial cells compared with wild-type endothelium. Taken together, these results demonstrate that vascular Gas6 contributes to thrombus formation in vivo and can be explained by the ability of Gas6 to promote tissue factor expression and activity. These findings support the notion that vascular wall-derived Gas6 may play a pathophysiologic role in venous thromboembolism.
- Subjects :
- Animals
Blood Platelets metabolism
Blood Vessels pathology
Endothelial Cells metabolism
Gene Expression Regulation
Intercellular Signaling Peptides and Proteins metabolism
Male
Mice
Mice, Knockout
Thromboplastin metabolism
Thrombosis metabolism
Blood Vessels metabolism
Intercellular Signaling Peptides and Proteins genetics
Thromboplastin genetics
Thrombosis genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 121
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 23149844
- Full Text :
- https://doi.org/10.1182/blood-2012-05-433730