Department of Cardiac Surgery, Second Hospital Affiliated to Hebei Medical University, Shijiazhuang, Hebei Province, China.
Eur Rev Med Pharmacol Sci. 2020 Mar;24(5):2725-2737. doi: 10.26355/eurrev_202003_20545.
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.
最近的研究表明，长非编码 RNA 参与动脉粥样硬化的形成，这是冠心病的病理基础。在这里，我们报道了 RMRP 在冠状动脉粥样硬化中的功能和调节机制。
qPCR 用于研究冠状动脉粥样硬化和人血管平滑肌细胞中 IL-6、IL-8、RMRP 和 miR-128-1-5P 的表达。荧光素酶报告实验证实了 RMRP 与 miR-128-1-5P 以及 miR-128-1-5P 与 Gadd45g 在 HEK293T 中的直接靶标效应。Western blot 用于检测冠状动脉粥样硬化和人血管平滑肌细胞中的蛋白表达。
RMRP 表达和 Gadd45g 蛋白水平在冠状动脉粥样硬化和人血管平滑肌细胞中上调，而 miR-128-1-5P 下调。RMRP 下调显著抑制 ox-LDL 处理后人血管平滑肌细胞中 IL-6、IL-8 和凋亡相关蛋白的表达。此外，生物信息学分析和荧光素酶报告实验证实，RMRP 是 miR-128-1-5P 的直接靶标。此外，miR-128-1-5P 抑制剂在 ox-LDL 处理人血管平滑肌细胞后明显保留了 RMRP-si 诱导的 IL-6、IL-8 和凋亡相关蛋白的作用，表明 RMRP 负向且直接调节冠状动脉粥样硬化中的 miR-128-1-5P。更重要的是，RMRP 沉默增加了人血管平滑肌细胞中的 Gadd45g 蛋白水平。在 ox-LDL 处理人血管平滑肌细胞并进行 miR-128 上调后，也发现了相同的结果。同时，Gadd45g-si 极反转了 ox-LDL 处理人血管平滑肌细胞后 miR-128-1-5P 抑制剂诱导的 IL-6、IL-8 和凋亡相关蛋白的结果，荧光素酶报告实验表明 Gadd45g 是 miR-128-1-5P 的直接靶标，表明 Gadd45g 负向且直接调节冠状动脉粥样硬化中的 miR-128-1-5P。此外，利拉鲁肽明显抑制冠状动脉粥样硬化中 IL-6、IL-8 和凋亡相关蛋白的表达。总之，这些结果表明利拉鲁肽可以通过调节 RMRP/miR-128-1-5P/Gadd45g 信号通路来改善冠状动脉粥样硬化。
利拉鲁肽通过调节 RMRP/miR-128-1-5P/Gadd45g 信号通路，可以抑制冠状动脉粥样硬化中炎症细胞因子和凋亡相关蛋白的表达，为冠状动脉粥样硬化的治疗提供了新的潜在策略。
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