Fucoxanthin prevents septic cardiomyopathy by targeting BRD2 in M1-polarized macrophages

Septic cardiomyopathy (SCM) leads to heart failure, with few effective approaches for its intervention. Fucoxanthin (FX) possesses anti-inflammatory capacity, but its effect on SCM remains unknown. Herein, we report that FX protects against cardiac dysfunction in a lipopolysaccharide (LPS)-induced mouse model of sepsis with a dramatic reduction of inflammatory cell infiltration in the heart tissue. The analysis of human and mouse databases revealed M1-polarized macrophages as the most evidently infiltrated immune cells into the heart tissue under septic conditions. This phenomenon was found in the current mouse model, which was significantly inhibited by FX. FX blunted macrophage M1 polarization <i>in vitro</i> that provoked inflammation in cardiomyocytes. Further, bromodomain-containing protein 2 (BRD2) was predicted as a molecular target of FX. Moreover, FX decreased BRD2 protein in both mouse hearts and macrophages in the presence of LPS. BRD2 overexpression abolished FX's macrophage-silencing effect. Notably, FX decreased BRD2 levels and inhibited inflammation in peripheral monocyte-derived macrophages from patients with SCM. The present study offers FX and BRD2 as a novel approach and molecular target for SCM intervention.