Hypercoagulation in Patients with Rheumatoid Arthritis Correlates with Activation of Act1/NF-κb Signaling Pathway

Abstract

Objective: To explore the role of the Act1/NF-κB signaling pathway in the development of hypercoagulation states in patients with rheumatoid arthritis (RA). Methods: Peripheral blood samples were taken from 30 RA patients and 20 healthy volunteers, as controls. Ex vivo correlates of disease severity, such as C-reactive protein, erythrocyte sedimentation rate, anti-cyclic citrullinated peptide and rheumatoid factor, and immunological activation, such as interleukin (IL)-10, IL17 and IL-6 were measured biochemically. Factors derived from the coagulation fibrinolytic system were also determined, such as the number of platelets, platelet activating factor, platelet activating factor-acetylhydrolase, D-dimer, thrombin time, prothrombin time, partial thromboplastin time, and fibrinogen levels. Furthermore, analysis of NF-κB signaling molecules Act1, p65, p50, IκBα and IκB kinase α (IKKα) was performed using semi-quantitative reverse transcription and western blotting. Results: Compared with the healthy control group, the levels of D-dimer, fibrinogen, and the number of platelets were significantly increased in the peripheral blood of RA patients, whereas partial thromboplastin time and thrombin time were decreased. IL-4, IL10 and PAF-AH were significantly decreased in the serum of RA patients, while IL-6, IL-17, Act1, p50, p65, IκBα and PAF were significantly increased. Multiple regression analysis showed that coagulant and fibrinolytic indexes correlated significantly with cytokines, NF-κB, activity indexes and clinical symptoms. Conclusion: Hypercoagulation state was prevalent in patients with RA and was related to inflammatory factors, activity indexes and activation of NF-κB. The results suggested that abnormal activation of the NF-κB signaling pathway and an imbalance of proand anti-inflammatory cytokines was the result of a disturbance in the coagulation-fibrinolytic system.