NGAL contributes to hemostasis and thrombosis by potentiating or suppressing coagulant or anticoagulant factors

Coagulation is related to inflammation, but the key pathways, especially innate immunity inflammatory response-coagulation, hemostasis, and thrombus regulation is poorly understood and need to be further explored. In the current study, we showed that innate immunity inflammatory mediator neutrophil gelatinase-associated apolipoprotein (NGAL) interacted with and potentiated thrombin, kallikrein, and FXIa and suppressed the inactivation of thrombin by antithrombin to induce hypercoagulability. Furthermore, NGAL can augment thrombin-induced platelet aggregation. In multiple mice hemostasis and thrombus models, NGAL overexpression or intravenous administration promoted hemostasis and aggravated thrombotic tendency, whereas NGAL knockout or treatment with anti-NGAL monoclonal antibody significantly prolonged bleeding time and alleviated thrombus formation. Importantly, NGAL knockout prolonged mice tail bleeding time or artery occlusion time to over 40 min or 30 min, respectively. Furthermore, anti-NGAL monoclonal antibody treatment significantly alleviated thrombus formation in mice-tail thrombosis model induced by carrageenan, which is associated with inflammation. Collectively, these findings clarify NGAL is an important coagulation regulator and mediates the crosstalk between innate immunity inflammation and coagulation, hemostasis, and thrombus, and provide new targets and strategies for the development of safe and efficient innovative antithrombotic drugs. ### Competing Interest Statement The authors have declared no competing interest.