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

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.