Hereditary angioedema: key role for kallikrein and bradykinin in vascular endothelial-cadherin cleavage and edema formation.

摘要

Hereditary angioedema (HAE) is characterized by recurrent episodes of edema that can be life-threatening if not treated properly.1 It is an autosomal-dominant inherited disease caused by Cl inhibitor deficiency as a result of mutations in the SERP-ING1 gene. Because of Cl inhibitor deficiency in HAE, the plasma proteolytic cascades are activated during an attack (plasma kallikrein and coagulation factor Xlla) and kinins are generated. Among these, bradykinin has been shown to be the predominant mediator of enhanced vascular permeability in HAE attacks.2'3 Microvascular permeability is tightly controlled by a series of complex interactions between junctional proteins.4 In the endothelium, adherens junctions are formed by the transmem-brane adhesive protein vascular endothelial (VE)-cadherin.4 The integrity of the endothelial cell-cell junction depends on the adhesive function and cell surface expression of VE-cadherin.5 Previous studies have demonstrated that disruption of cell-cell junctions depends on VE-cadherin tyrosine phosphorylation or cleavage.6 Therefore, we explored whether VE-cadherin was involved in the pathogenesis of HAE.