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 NETs levels and its role in the induction of procoagulant activity (PCA) in EH, as well as to evaluate its interactions with platelets or endothelial cells (ECs). Methods The levels of NETs in the plasma of study subjects were detected by ELISA. NET formation and the morphology of cells were analysed using immunofluorescence or electron. PCA was analysed by purified coagulation complex assays, clotting time and fibrin turbidity. Phosphatidylserine (PS) exposured 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 NETs formation in vitvo. 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.