Coagulation activation plays a pivotal role in the pathogenesis of VTE and experimental (in vitro and in vivo animal models) have demonstrated a substantial interplay between the coagulation and complement cascade systems. We hypothesize that dysregulated complement factors, and in particular components of the lectin pathway, may facilitate coagulation activation and thereby influence VTE risk.
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)
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