Inflammatory cytokines induce neutrophil extracellular traps interaction with activated platelets and endothelial cells exacerbate coagulation in moderate and severe essential hypertension

BACKGROUND: Essential hypertension (EH) patients suffer from paradoxically thrombotic rather than haemorrhagic, although the exact mechanism remains elusive. Our aim is to explore whether and how neutrophil extracellular traps (NETs) play the procoagulant role in EH patients, as well as evaluated whether the NET releasing were triggered by inflammatory cytokines. METHODS: The concentration of plasma NETs components were detected by ELISA. The morphology of cells and NETs formation were analysed using immunofluorescence. Procoagulant activity was analysed by clotting time, purified coagulation complex and fibrin generation assays. Phosphatidylserine (PS) exposure on endothelial cells (ECs) was analysed with flow cytometry. RESULTS: Moderate to severe EH patients plasma NETs levels were significantly higher compared to mild EH patients or controls. Furthermore, inflammatory cytokines can induce NETs generation, depleting these patients plasma inflammatory cytokines led to a reduction in NET releasing. NETs from moderate to severe EH patients neutrophils led to significantly decreased clotting time (CT), increased potency to generate thrombin and fibrin (all P < 0.05). These procoagulant effects were markedly attenuated by approximately 70% using DNase I. Additionally, high concentrations NETs exerted a strong cytotoxic effect on ECs, conferring them a procoagulant phenotype. CONCLUSION: Our study reveals that EH drives a systemic inflammatory environment, which, in turn, drives neutrophils to prime and NET releasing, and found a link between hypercoagulability and NETs levels in moderate to severe EH patients. Therefore, anti-inflammatory combined with block the generation of NETs may represent a new therapeutic target for preventing thrombosis in EH patients.