Hsa-miR-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis.
2020
Of the known regulators of atherosclerosis, miRNAs have been demonstrated to play critical roles in lipoprotein homeostasis and plaque formation. Here, we generated a novel animal model of atherosclerosis by knocking-in LDLRW483X in C57BL/6 mice, as the W483X mutation in LDLR is considered the most common, newly identified pathogenic mutation in Chinese familial hypercholesterolemia (FH) individuals. Using the new in vivo mouse model combined with a well-established atherosclerotic in vitro human cell model, we identified a novel atherosclerosis related miRNA, miR-23a-3p by microarray analysis of mouse aorta tissue specimens and human aorta endothelial cells (HAECs). MiR-23a-3p was consistently downregulated in both models, which was confirmed by qPCR. Bioinformatics analysis and further validation experiments revealed that the TNFAIP3 gene was the key target of miR-23a-3p. The miR-23a-3p-related functional pathways were then analysed in HAECs. Collectively, the present results suggest that miR-23a-3p regulates inflammatory and apoptotic pathways in atherogenesis by targeting TNFAIP3 through the NF-κB and p38/MAPK signaling pathways.
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