Abstract 090: Slc44a2 Deficient Mice Exhibit Less Severity of Thrombosis in a Stenosis Model of Deep Vein Thrombosis
| Autor: | Bart J.M. van Vlijmen, Julia Tilburg, Gaia Zirka, Grace M. Thomas, Lieke van den Heijkant, Pierre Morange, Chrissta X Maracle |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Pathology
medicine.medical_specialty business.industry Deep vein Genome-wide association study medicine.disease Thrombosis Solute carrier family Stenosis medicine.anatomical_structure Susceptibility locus Deficient mouse Medicine Cardiology and Cardiovascular Medicine business Venous thromboembolism |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 38 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Background/Objective: Recent genome wide association studies identified SLC44A2 as a novel susceptibility locus for venous thromboembolism (VTE), a region encoding the solute carrier family 44 member 2 protein (SLC44A2). Here we utilize Slc44a2 deficient mice (KO) to determine the importance of SLC44A2 in thrombotic disease. Methods: Mice lacking Slc44a2 were included in two models of venous thrombosis: 1) a spontaneous thrombosis model using siRNA targeting anti-coagulants Serpinc1 and Proc and 2) a model of deep vein thrombosis (DVT) induced by flow restriction (stenosis) of the inferior vena cava (IVC). Results: In the model of spontaneous thrombosis, Slc44a2 deficiency did not affect incidence as occurrence of thrombotic phenotype reached 100% in both wild type (WT; 12/12) and KO (12/12) mice 32 hours after siRNA injection. Platelet counts and fibrin deposition in the liver were also comparable. However, levels of circulating neutrophils were significantly higher (p=0.0017) in KO mice along with substantially lower amounts of plasma VWF antigen (pSlc44a2 did (12/15). Thrombus length was significantly reduced in KO animals (p=0.0184), as was thrombus weight (p=0.0413). Immunhistochemical staining of the thrombi revealed different repartitions in the “white” (platelet-rich) over the “red” (RBC-rich) parts of the thrombi depending on the mouse genotype. This observation suggests a different blood cell mobilization at the site of stenosis depending of the genotype. Plasma VWF levels were correlated with thrombus weight in WT (p=0.0175), but not in KO mice (p=0.3266), and had been previously confirmed to be lower in KO mice. Conclusion: These findings corroborate the original GWAS data, indicating a role for SLC44A2 in thrombotic disease. We have observed that SLC44A2 was not involved in a platelet-dependent model of thrombosis whereas it is involved in a thrombosis model where neutrophils and VWF have been shown to play a crucial role. |
| Databáze: | OpenAIRE |
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