MiR-20a has been previously reported to participate in the development of various human diseases. However, the role of miR-20a in the pathology of atherosclerosis remains elusive. The present study aimed to reveal the relationship between miR-20a expression and atherosclerosis using in vitro cell model. The expression level of miR-20a was detected in human aortic endothelial cells (HAECs) under Ox-LDL exposure. Meanwhile, the regulatory effects of miR-20a on predicted targets (TLR4 and TXNIP) were also determined. Moreover, the levels of key proteins and inflammatory mediators in TLR4 and NLRP3 signaling were detected to further confirm the regulatory effects of miR-20a. We found that miR-20a expression was repressed under Ox-LDL condition, and both TLR4 and TXNIP acted as regulatory targets of miR-20a. Overexpressed miR-20a reduced ROS generation under Ox-LDL treatment, and this effect was restored by forced expression of TLR4. Moreover, key molecules (including MyD88, TRIF, phosphorylated NF-κB (p65), NLRP3, ASC, cleaved caspase-1, ICAM-1 and IL-1β) in TLR4 and NLRP3 signaling were significantly repressed under miR-20a overexpression. In conclusion, miR-20a could negatively regulate TLR4 and NLRP3 signaling to protect HAECs from inflammatory injuries, which provides a new insight into the inhibition of atherosclerotic development.
Keywords: Atherosclerosis; Inflammation; NLRP3; TLR4; miR-20a.
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