Neutrophil extracellular traps induced by pro-inflammatory cytokines enhance procoagulant activity in NASH patients - 12/01/22
, Jialan Shi a, e, f, ⁎ Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
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Highlights |
• | Our objectives were to study the NETs formation in NASH patients and to evaluate its procoagulant activity. |
• | Inflammatory cytokines promote NETs formation leading to procoagulant activity in NASH patients. |
• | NETs derived from NASH could dramatically shorten coagulation time and markedly increased the fibrin formation and TAT complexes. |
• | NASH-NETs convert HUVECs to procoagulant and pro-inflammatory phenotypes. |
• | Our findings demonstrated that NETs might play a important role in procoagulant activity in NASH, providing an ideal therapeutic strategy for attenuating inflammation and preventing the pathological hypercoagulable state of NASH patients. |
Summary |
Background |
Nonalcoholic steatohepatitis (NASH) patients are at a high risk of developing venous thromboembolism, with a high rate of morbidity and mortality. The role of neutrophil extracellular traps (NETs) in procoagulant activity (PCA) in patients with NASH remains unclear. Our study aimed to investigate the formation of NETs in NASH patients stimulated by specific pro-inflammatory factors. Moreover, we evaluated the pivotal role of NETs in the induction of hypercoagulability in NASH and the interaction between NETs and endothelial injury.
Method |
The levels of the NETs biomarkers were evaluated in the plasma samples of 27 NASH patients and 18 healthy subjects. The formation of NETs was visualized using immunofluorescence microscopy. The PCA of the NETs was assessed using coagulation time, purified coagulation complex, and fibrin formation assays. Confocal microscopy was further used to evaluate the interactions between the NETs and HUVECs.
Results |
The levels of NETs markers in the plasma of NASH patients were significantly higher than healthy controls. NETs derived from NASH enhanced thrombin and fibrin formation and significantly reduced CT (p<0.05). The mixture of IL-6 and TNF-α triggered the NETs release in the plasma rather than them alone. Additionally, the NETs exerted cytotoxic effects on the endothelial cells, converting them to a procoagulant and pro-inflammatory phenotype, and DNase I could reverse these effects.
Conclusion |
Our results revealed the primary role of NETs in promoting the hypercoagulable state in NASH patients. Methods that prevent the formation of NETs may be a novel approach for the prevention and treatment of NASH.
El texto completo de este artículo está disponible en PDF.Abbreviations : NASH, NETs, PCA, NAFLD, CVD, VTE, CT, BMI, AST, ALT, TBil, TC, TG, HDL, LDL, PT, aPTT, PAI-1
Keywords : neutrophil extracellular traps, procoagulant activity, NASH, inflammatory factors
Esquema
Vol 46 - N° 1
Artículo 101697- janvier 2022 Regresar al número
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Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
El acceso al texto completo de este artículo requiere una suscripción.
Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
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