High mobility group box 1 was associated with thrombosis in patients with atrial fibrillation

Abstract

INTRODUCTION: High mobility group box 1 (HMGB1) is a member of the HMGB family that is involved in inflammatory disease-related thrombosis. We hypothesize that HMGB1 and its downstream factors are associated with thrombosis in atrial fibrillation (AF). MATERIALS AND METHODS: Our experimental materials were the left atrial appendage (LAA) tissues from patients undergoing valve replacement. The samples were divided into 3 groups: a sinus rhythm group (n = 15), an AF(+)thrombus(-)group (n = 15), and an AF(+) thrombus (+)group (n = 15). The expression of HMGB1, Toll-like receptor 4 (TLR4), advanced glycation end product (RAGE), myeloid differentiation factor 88 (MyD88), nuclear factor κB (NFκB), p-NFκB, and tissue factor (TF) were detected by Western blot and immunohistochemical (IHC) staining. The expressions of interleukin-1 beta, interleukin 6, and tumor necrosis factor-alpha were detected by quantitative real-time PCR. RESULTS: The Western blots revealed significantly higher expressions of HMGB1, MyD88, p-NFκB/NFκB, and TF in the AF(+)thrombus(+) group than in the other 2 groups. However, no differences in TLR4 or RAGE expression were found between the groups. IHC staining also revealed higher expressions of HMGB1 and TF in the AF(+)thrombus(+) group. The increased mRNA expressions of classic inflammatory factors (i.e., interleukin-1 beta, interleukin 6, and tumor necrosis factor-alpha) in AF(+)thrombus(+) group further validated the correlation between inflammation and thrombi in atrial fibrillation. CONCLUSIONS: HMGB1 was associated with thrombosis in patients with AF via the MyD88/NFκB pathway after adjustment for cardiac and extra cardiac inflammation variables.