Semaglutide alleviates inflammation-Induced endothelial progenitor cells injury by inhibiting MiR-155 expression in macrophage exosomes.

The low-grade inflammatory state in obesity can damage vascular endothelial cells and lead to several cardiovascular diseases. Macrophage exosomes improve glucose tolerance and insulin sensitivity in obese mice, and yet it is unclear how it relates to endothelial cell injury. Firstly, lipopolysaccharide (LPS)-induced macrophage exosomes were co-cultured with endothelial progenitor cells (EPCs) to examine the function of EPCs and the level of inflammatory factors. Secondly, macrophages were transfected with MicroRNA-155 (miR-155) miR-155 mimics and inhibitors, and their secreted exosomes were co-cultured with EPCs to detect EPCs function and inflammatory factor levels. Then, EPCs were transfected with miR-155 mimics and inhibitors to clarify the effect of miR-155 on EPCs function and inflammatory factors. Finally, macrophages were intervened using semaglutide, and their secreted exosomes were co-cultured with EPCs to test EPCs function, inflammatory factor levels and macrophages miR-155 expression. LPS-induced macrophage exosomes reduced the cellular activity, migratory capacity and tube-forming ability of EPCs and rendered EPCs in an inflammatory state. LPS-induced microphage exosomes significantly upregulated miR-155 expression. miR-155 high expression exacerbated the pro-inflammatory nature of macrophage exosomes and inhibited the cell viability of EPCs. In contrast, inhibition of miR-155 expression showed the opposite result, suppressing inflammation and increasing the cell viability of EPCs. Semaglutide improved the cell viability of EPCs and also inhibited the expression of inflammatory factors in EPCs as well as miR-155 in exosomes. Semaglutide improves the function and inflammatory status of EPCs may via inhibition of LPS-induced macrophage expression of miR-155 in exosomes.