However, C1-inhibitor is also the primary inhibitor of MASP-1, therefore, our results suggest an additional pathogenetic pathway in HAE: in the absence of sufficient amount of C1-inhibitor, MASP-1 is over-activated upon microbial infection, trauma or sterile inflammation, forms bradykinin by cleaving kininogen and up-regulate BDKRB2 on endothelial cells, which together contribute to the increased permeability leading to the life-threatening edematous attacks. This evidence concerns the gene KNG1 and hereditary angioedema.