Role of the complement system in venous thrombosis
The complement system is an important part of the innate immune system and serves as first line of defense. Complement can be activated via three pathways: (i) the classical, (ii) the lectin and (iii) the alternative pathways. Of particular note, the complement system has several points of interplay with the coagulation system, mostly via the lectin pathway, which may potentially contribute to a prothrombotic phenotype upon complement activation. Growing evidence suggest that components of the complement system are associated with venous thromboembolism (VTE). The principle scientific approach in this presentation will be to; (i) identify associations between components of the lectin complement pathway and VTE risk in cohort studies, (ii) explore whether lectin pathway components associated with VTE are genetically regulated (using plasma quantitative trait loci (pQTL) analysis), (iii) perform Mendelian randomization analysis to uncover potential causal relationships between biomarkers and VTE risk (if components are genetically regulated), (iv) explore underlying mechanism(s) in experimental models in vivo (mouse model) and in vitro (coagulation assays and activation of endothelial cells).