Milestone VTE

In this project, we hypothesize that a circulatory imbalance between lectin pathway activators (e.g. MBL and subsequent MASP-2 activation) and inhibitors (e.g. C1-INH) facilitates thrombus formation. In a translation approach, we will integrate omics data (proteomics and genomics) on lectin and coagulation pathway components, derived from unique high-quality population-based cohorts with validated VTE registries (i.e., the HUNT and Tromsø studies), with cutting-edge in vitro and in vivo experimental model systems to (i) identify modifiable biomarkers causally related to VTE and (ii) to unravel molecular pathways involved in the pathogenesis of VTE. The results of the project may improve risk assessment and targeted prevention and thereby contribute to diminish the suffering and burden of VTE in the society. 

Principal Investigator: John-Bjarne Hansen

External collaborators: Steven P. Grover, Nigel Mackman (University of North Carolina Chapel Hill); Tom Eirik Mollnes (Norwegian Complement Research Group, UiO)

Publications:

Grover et al. C1 inhibitor deficiency enhances contact pathway-mediated activation of coagulation and venous thrombosis. Blood 2023;141:2390-2401.

Grover et al. High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism. JTH 2023;21:1849-60.

Skjeflo et al. Complement factors B, D, C3bBbP and risk of future venous thromboembolism. Clin Immunol. 2023;249:109278

Damoah et al. High Levels of Complement Activating Enzyme MASP-2 Are Associated With the Risk of Future Incident Venous Thromboembolism. Arterioscler Thromb Vasc Biol. 2022; 42: 1186-97.

Skjeflo et al. Elevated plasma concentration of complement factor C5 is associated with risk of future venous thromboembolism. Blood. 2021;138:2129-37

Liang et al. Plasma levels of mannose-binding lectin and future risk of venous thromboembolism. J Thromb Haemost. 2019; 17: 1661-9

Hoiland et al. Complement activation assessed by the plasma terminal complement complex and future risk of venous thromboembolism. J Thromb Haemost. 2019; 17: 934-43

Hoiland et al. Associations between complement pathways activity, mannose-binding lectin, and odds of unprovoked venous thromboembolism. Thromb Res. 2018; 169: 50-6.