MiR‐181a inhibits vascular inflammation induced by ox‐LDL via targeting TLR4 in human macrophages

• Published in: Journal of cellular physiology Vol. 233; no. 10; pp. 6996 - 7003
• Main Authors: Du, Xian‐Jin, Lu, Jing‐Min, Sha, Yin
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-10-2018
• Subjects: Apoptosis; Arteriosclerosis; Atherosclerosis; Blood vessels; CD36 antigen; IL-1β; Inflammation; Linings; Low density lipoprotein; Macrophages; miRNA; miR‐181a; ox‐LDL; Proteins; TLR4; TLR4 protein; Toll-like receptors; Tumor necrosis factor; atherosclerosis; ox-LDL; miR-181a; TLR4
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.26622

Atherosclerosis is a kind of chronic inflammation disease with lipid accumulation in in blood vessel linings. Increasing evidence has reported that microRNAs can exert crucial roles in atherosclerosis. In previous study, miR‐181a has been implicated to be abnormally expressed in atherosclerosis mice, however its detailed function in atherosclerosis remains uninvestigated. Hence, in our current study, we focused on the biological role of miR‐181a in atherosclerosis progression. Ox‐LDL has been commonly identified as an important atherosclerosis regulator. We observed that ox‐LDL induced THP‐1 cell apoptosis dose‐dependently and time‐ dependently. Meanwhile, 25 µg/ml ox‐LDL can promote foam cell formation and increased miR‐181a expression significantly. CD36 has been involved in atherosclerosis progression and it was found that overexpression of miR‐181a inhibited its protein levels. Moreover, miR‐181a mimics repressed foam cell formation, TC and TG levels induced by ox‐LDL dramatically. In addition, miR‐181a mimics were able to reverse THP‐1 cell apoptosis, increased IL‐6, IL‐1β, and TNF‐α protein expression triggered by 25 µg/ml ox‐LDL. TLR4 has been linked to various inflammation‐associated diseases. In our present study, TLR4 was indicated as miR‐181a target and the binding correlation between them was validated by dual‐luciferase reporter assay. In conclusion, these results improves the understanding of atherosclerosis modulated by miR‐181a/TLR4 and can contribute to development of new approaches for atherosclerosis.
We found that miR‐181a can inhibit atherosclerosis events in THP‐1 cells and that miR‐181a overexpression inhibited cell inflammation and cell apoptosis through targeting TLR4. The negative correlation between miR‐181a and TLR4 was predicted and confirmed. Our findings revealed that miR‐181a restrained atherosclerosis development via targeting TLR4 in vitro.