miR-126-5p promotes M1 to M2 macrophage phenotype switching via VEGFA and KLF4

<strong>Background. </strong>Macrophage polarization plays an important role in the regression of atherosclerosis (AS), a chronic inflammatory disease. However, the exact mechanisms mediated by microRNA-126 (miR-126) are not fully understood. <strong>Methods.</strong> A miR-126-5p intervention foam cell model was established a by stimulating the human monocytic cell line with oxidized low-density lipoprotein (ox-LDL). The levels of miR-126 and M1/M2 associated genes in foam cells were quantified using reverse transcription-quantitative PCR (RT-qPCR). Additionally, the expression of CD86⁺ and CD206⁺ cells in foam cells was determined by flow cytometry. Western blotting and RT-qPCR were used to determine the protein and mRNA levels of the vascular endothelial growth factor (VEGFA) and the transcriptional regulator Krüppel-like factor 4 (KLF4), respectively. <strong>Results. </strong>The activation of apoptosis and production of foam cells was boosted by the addition of ox-LDL. The resulting macrophages were transfected with a miR-126-5p mimic and a negative control. And miR-126-5p greatly suppressed foam cells development and inhibited phagocytosis. Moreover, it caused pro-inflammatory M1 macrophages switching to the anti-inflammatory M2 phenotype. This was reflected by the increase in anti-inflammatory gene expression and pro-inflammatory gene suppression. And miR-126-5p dramatically decreased the expression of VEGFA and KLF4. The protein–protein interaction network analysis,showed a significantly high correlation between miR-126-5p, VEGFA, and KLF4. <strong>Conclusion.</strong> Our study shows that miR-126-5p can reverse ox-LDL-mediated phagocytosis and apoptosis in macrophages. As a result, miR-126-5p represents a potential role in the regulation of macrophage function and prevention of cardiovascular complications arising from atherosclerosis.