Decreased serum HMGB1 associated with M2 macrophagepolarization and patients with calcific aortic valve disease

摘要

Except for the standard aortic valve replacement,no effective medical treatment is available to prevent or delay calcific aortic valve disease(CAVD)progression.Recently,macrophages and high-mobility group box 1(HMGB1)are the most intriguing candidates in various inflammatory disorders.However,the association between serum HMGB1,CAVD,and macrophage polarization remains unclear.Therefore,we examined whether the level of serum HMGB1 is clinically associated with aortic valve calcification and whether HMGB1 treatment can promote macrophage differentiation toward M1 or M2 phenotype.This experimental study included 19 CAVD patients and 20 healthy controls whose serum HMGB1 levels were examined by ELISA assay.THP-1 macrophage polarization system was established to test the polarization capability of HMGB1 treatment.The results showed that serum levels of HMGB1 were significantly reduced in patients with CAVD.HMGB1 treatment promoted M2 macrophage polarization but not M1 phenotype with increased IL-10 expression and reduced inducible nitric oxide synthase(iNOS)expression.Our findings suggest that serum HMGB1 is negatively associated with the development of aortic valve calcification,and HMGB1 treatment may facilitate M2 macrophage polarization for reducing aortic valve calcification.