WPB constituents and their link with VT
| WPB constituent . | Effect on VT . | Mechanism . | Phenotype in mutant mice . | Reference . |
|---|---|---|---|---|
| VWF | ↑ | Mediates recruitment of leukocytes and platelets to the site of thrombosis. At low shear rate, recruits leukocytes through PSGL-1 and β2-integrin and supports firm adhesion. Binds to macrophages leading to modified expression of over a thousand inflammation-related genes, which could contribute to additional endothelial activation and leukocyte recruitment to the site of thrombosis. | Confirmed | 14-19 |
| P-selectin | ↑ | Mediates leukocyte recruitment to the thrombosis site. Reportedly anchors released VWF multimers to the endothelial surface, although this was disputed in another study. | Confirmed | 15,20,21 |
| Eotaxin | ↑ | Chemoattractant for eosinophils, increases the permeability and oxidative stress in ECs, supports inflammation through eosinophil recruitment, MC degranulation, and blood clotting. Eosinophils stimulate the release of VWF from ECs leading to recruitment and activation of platelets by major basic protein. Hypereosinophilia is a risk factor for VTE. | Not confirmed | 22-25 |
| Angiopoietin-2 | ↑ | Increases thrombus size after 3-d IVC ligation. Reduces plasma levels of activated protein C. Hypoxia strongly enhances the expression of Ang-2 messenger RNA in human endothelium, and plasma levels correlate with the severity of pulmonary embolism. | Confirmed | 26-28 |
| Endothelin-1 | TBD | Induces vasoconstriction and stimulates the production of NO and PGI2. | Not confirmed | 29 |
| Osteoprotegerin | TBD | Binds to A1 VWF domain and prevents platelet adhesion to VWF strings. | Not confirmed | 30,31 |
| WPB constituent . | Effect on VT . | Mechanism . | Phenotype in mutant mice . | Reference . |
|---|---|---|---|---|
| VWF | ↑ | Mediates recruitment of leukocytes and platelets to the site of thrombosis. At low shear rate, recruits leukocytes through PSGL-1 and β2-integrin and supports firm adhesion. Binds to macrophages leading to modified expression of over a thousand inflammation-related genes, which could contribute to additional endothelial activation and leukocyte recruitment to the site of thrombosis. | Confirmed | 14-19 |
| P-selectin | ↑ | Mediates leukocyte recruitment to the thrombosis site. Reportedly anchors released VWF multimers to the endothelial surface, although this was disputed in another study. | Confirmed | 15,20,21 |
| Eotaxin | ↑ | Chemoattractant for eosinophils, increases the permeability and oxidative stress in ECs, supports inflammation through eosinophil recruitment, MC degranulation, and blood clotting. Eosinophils stimulate the release of VWF from ECs leading to recruitment and activation of platelets by major basic protein. Hypereosinophilia is a risk factor for VTE. | Not confirmed | 22-25 |
| Angiopoietin-2 | ↑ | Increases thrombus size after 3-d IVC ligation. Reduces plasma levels of activated protein C. Hypoxia strongly enhances the expression of Ang-2 messenger RNA in human endothelium, and plasma levels correlate with the severity of pulmonary embolism. | Confirmed | 26-28 |
| Endothelin-1 | TBD | Induces vasoconstriction and stimulates the production of NO and PGI2. | Not confirmed | 29 |
| Osteoprotegerin | TBD | Binds to A1 VWF domain and prevents platelet adhesion to VWF strings. | Not confirmed | 30,31 |
Ang-2, angiopoietin-2; PGI2, prostaglandin I2; TBD, to be determined.