Polyphosphate-induced thrombosis in mice is factor XII dependent and is attenuated by histidine-rich glycoprotein.

ABSTRACT: Histidine-rich glycoprotein (HRG) is an abundant plasma protein that binds factor XIIa (FXIIa) and inhibits factor XII (FXII) autoactivation and FXIIa-mediated activation of FXI. Polyphosphate (polyP), a potent procoagulant released from activated platelets, may serve as a physiological activator of the contact system. Previously, we showed that HRG binds DNA and neutralizes its procoagulant activity. Consequently, our goal was to determine whether the capacity of HRG to bind polyanions enables it to regulate polyP-induced thrombosis. In a plate-based assay, immobilized polyP bound HRG, FXII, and FXIIa in a zinc-dependent manner. Basal and polyP-induced thrombin generation was greater in plasma from HRG-deficient mice than in plasma from wild-type mice. Intraperitoneal injection of polyP s

SUBMITTER: Malik RA 

PROVIDER: S-EPMC8945577 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature