Neutrophil Extracellular Traps Enhance Procoagulant Activity In Patients With Essential Hypertension

Background: Essential hypertension (EH) patients, especially those along with hyperhomocysteinemia (HHcy), suffer from increased thrombotic events; however, the underlying mechanism remains unclear to date.Objective: We aimed to measure the plasma neutrophil extracellular trap (NET) levels and their role in the induction of procoagulant activity (PCA) in EH, as well as to evaluate the interactions with platelets or endothelial cells (ECs).Methods: The levels of NETs in the plasma of study subjects were detected by enzyme-linked immunosorbent assay. NET formation and the morphology of cells were analyzed using immunofluorescence or electron microscopy. PCA was analyzed by purified coagulation complex assays, clotting time, and fibrin turbidity. Phosphatidylserine (PS) exposure on ECs was detected with flow cytometry.Results: We observed that cell free-DNA and myeloperoxidase-DNA were significantly higher in EH patients compared to healthy controls. Moreover, NET formation was positively correlated with serum homocysteine (Hcy) levels in EH with HHcy. Furthermore, neutrophils from EH patients were more prone to produce NETs compared to those from controls. More importantly, immunofluorescence showed that HHcy could induce NET formation in vitro. Coagulation function assays showed that EH NETs significantly shortened coagulation time and increased thrombin and fibrin generation. The PCA was markedly attenuated approximately 70% by using DNase I. Additionally, isolated NETs from EH neutrophils induced platelet activation, exerted a strong cytotoxic effect on ECs, and converted them to a procoagulant phenotype.Conclusions: Our study revealed a previously unrecognized link between hypercoagulability and NETs in EH. Therefore, blocking NETs may represent a new therapeutic target for preventing thrombosis in these patients.