MicroRNA-3614 regulates inflammatory response via targeting TRAF6-mediated MAPKs and NF-κB signaling in the epicardial adipose tissue with coronary artery disease

Objective: The inflammatory status of epicardial adipose tissue (EAT) is one of the factors leading to the development of related diseases such as coronary artery disease (CAD). The thickness of CAD EAT increases and is accompanied with increased macrophage infiltration and heightened inflammatory responses. However, microRNAs (miRNAs) regulating the inflammatory responses of macrophages in CAD EAT remain unclear. Method: miRNA expression profiles of CAD EATs and non-CAD EATs were determined by miRNA microarrays. Quantitative real-time reverse transcription-polymerase chain reaction, Western blotting, immunohistochemical assay, and fluorescence in-situ hybridization were adopted to detect miR-3614 expression and function in EATs and macrophages. The interaction between miR-3614 and tumor necrosis factor receptor-associated factor 6 (TRAF6) was identified using an online website combined with a dual-luciferase reporter assay. Enzyme-linked immunosorbent assay was performed to detect the expression of inflammatory cytokines. Results: The decreased expression of miR-3614 was identified in CAD EAT. The level of miR-3614 was down-regulated by lipopolysaccharide (LPS) in macrophages, whereas LPS-induced inflammatory injury can be reduced by miR-3614 overexpression. TRAF6 was predicted and verified to be a target of miR-3614. The phosphorylated levels of kinases in the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B pathways were inhibited by miR-3614 overexpression. Importantly, the knockdown of TRAF6 inhibited the LPS-induced inflammatory cytokine expressions in cells. Conclusion: A novel negative feedback loop by miR-3614 possibly contribute to the regulation of inflammatory processes via targeting the TRAF6/MAPK/NF kappa B pathway in EATs and prevents an overwhelming inflammatory response. (C) 2020 Published by Elsevier B.V.

Automated summary

The decreased expression of miR-3614 in CAD EAT contributes to the regulation of inflammatory processes via targeting the TRAF6/MAPK/NF-kappa B pathway, preventing an overwhelming inflammatory response.