A predominant role of platelet NLRP3 in deep vein thrombosis in mice.

Abstract

Background: Inflammation-induced injury of venous endothelium is the first trigger of deep vein thrombosis (DVT). We previously showed NLRP3 regulates platelet function and arterial thrombosis. However, whether platelet NLRP3 involves in venous thrombosis remains unclear.

Objectives: In the present study, we intend to investigate the role of NLRP3 in venous thrombosis by using NLRP3 knockout mice and platelet-specific NLRP3 knockout mice.

Methods: Deep vein thrombosis (DVT) model was established through ligation of the inferior vena cava (IVC). 48 hours after ligation, IVC sample was excised to measure thrombi length and weight, the recruitment of platelets, neutrophils, monocytes, and neutrophil extracellular traps (NET) formation by immunofluorescence staining.

Results: Deficiency of NLRP3 reduced the incidence and severity of venous thrombosis, inhibited the recruitment and accumulation of platelets, neutrophils and monocytes in venous thrombi, reduced NET formation as well as IL-1β and IL-18 release. Additionally, platelet NLRP3 is the major source of elevated IL-1β in the venous thrombi and adoptive transfer of platelets to NLRP3^-/- mice increased IL-1β level in thrombi, promoted venous thrombosis and NET formation. Moreover, platelet NLRP3 deficiency inhibited NET formation induced by activated platelets in vitro.

Conclusions: Our study demonstrates that deficiency of NLRP3 reduces the incidence and the severity of venous thrombosis with platelet NLRP3 playing a predominant role, indicating that NLRP3 might be a therapeutic target for the treatment of venous thrombosis.