Liraglutide improves atherosclerosis by regulating long non-coding RNA RMRP/miR-128-1-5P/Gadd45g axis

Recent studies indicated that long non-coding RNA is involved in the formation of atherosclerosis, which is the pathological basis of coronary heart disease. Here, we reported the function and regulatory mechanism of RMRP in coronary atherosclerosis.

qPCR was used to investigate the expression of IL-6, IL-8, RMRP, and miR-128-1-5P in coronary atherosclerosis and human vascular smooth muscle cells. Luciferase reporter assay confirmed the direct target effect of RMRP with miR-128-1-5P and miR-128-1-5P with Gadd45g on HEK293T. Western blot was used to detect protein expression in coronary atherosclerosis and human vascular smooth muscle cells.

RMRP expression and Gadd45g protein level were up-regulated in coronary atherosclerosis and human vascular smooth muscle cells, while miR-128-1-5P was down-regulated. RMRP downregulation remarkably inhibited the expression of IL-6, IL-8, and apoptosis related protein in human vascular smooth muscle cells after ox-LDL treatment. In addition, bioinformatics analysis and Luciferase report experiments confirmed that RMRP was the direct target of miR-128-1-5P. Moreover, miR-128-1-5P inhibitor reserved evidently the effect of IL-6, IL-8, and apoptosis related protein induced RMRP-si after treatment of human vascular smooth muscle cells with ox-LDL, implying RMRP negatively and directly regulated miR-128-1-5P in coronary atherosclerosis. More importantly, RMRP silencing increased Gadd45g protein level in human vascular smooth muscle cells. The same results were found when miR-128 was upregulated. Meanwhile, Gadd45g-si extremely reversed the result of IL-6, IL-8, and apoptosis related protein induced miR-128-1-5P inhibitor after treatment of human vascular smooth muscle cells with ox-LDL and Luciferase report experiments showed that Gadd45g was a direct target of miR-128-1-5P, implying Gadd45g negatively and directly regulated miR-128-1-5P in coronary atherosclerosis. Furthermore, liraglutide restrained evidently the expression of IL-6, IL-8, and apoptosis related protein in coronary atherosclerosis. After all, these results showed that liraglutide could regulate RMRP/miR-128-1-5P/Gadd45g signal pathway to improve coronary atherosclerosis.

Liraglutide could curb the expression of inflammatory cytokines and apoptosis related protein in coronary atherosclerosis by regulating RMRP/miR-128-1-5P/Gadd45g signaling pathway, providing a new potential strategy for the treatment of coronary atherosclerosis.