Blocking domain 6 of high molecular weight kininogen to understand intrinsic clotting mechanisms.

ABSTRACT:

Background

The contact system is initiated by factor (F) XII activation and the assembly of high molecular weight kininogen (HK) with either FXI or prekallikrein (PK) on a negatively charged surface. Overactivation of this system contributes to thrombosis and inflammation in numerous diseases. To develop effective therapeutics for contact system disorders, a detailed understanding of this pathway is needed.

Methods

We performed coagulation assays in normal human plasma and various factor-deficient plasmas. To evaluate how HK-mediated PK and FXI activation contributes to coagulation, we used an anti-HK antibody to block access to domain 6 of HK, the region required for efficient activation of PK and FXI.

Results

FXI's binding to HK and its subsequent activation by acti

SUBMITTER: Singh PK 

PROVIDER: S-EPMC9561425 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature