KLF7 promotes macrophage activation by activating the NF-κB signaling pathway in epicardial adipose tissue in patients with coronary artery disease.

Abstract

Inflammatory accumulation in epicardial adipose tissue (EAT) may influence the formation and development of coronary artery disease (CAD). EAT macrophages exhibit M1 polarization and the secretion of a large number of inflammatory factors in CAD patients. Emerging data demonstrate that Krüppel-like factor-7 (KLF7), contributes to the regulation of adipocyte differentiation and the secretion of adipose tissue inflammation. However, the function of KLF7 in EAT inflammation still remains to be uncovered. This study aims to investigate the role of KLF7 in macrophage activation in EAT. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels were measured by Real Time-PCR. The protein expression level was detected by Western blot. The expression of inflammatory factors and KLF7 were markedly increased in CAD EAT than non-CAD EAT. KLF7 is highly expressed in human THP-1-derived macrophages induced by inflammatory stimuli, such as LPS. The knockdown of KLF7 inhibited the release of inflammatory factors and significantly decreased the expression of KLF7 in human THP-1-derived macrophages stimulated by LPS. Moreover, transfection with KLF7-siRNA caused the marked inhibition of LPS-induced phosphorylation of JNK-MAPKs and also suppressed the levels of p-p65 and inhibited the activation of p-IκBα. Taken together, these results indicate that KLF7 enhances macrophage activation, mediated by JNK-NF-κB signaling pathways in EAT. This suggests that KLF7 may be a potential therapeutic target for cardiovascular diseases such as CAD.