Protective effect of microRNA‑381 against inflammatory damage of endothelial cells during coronary heart disease by targeting CXCR4

Li,Yimin; Huang,Jin; Yan,Hong; Li,Xiangyu; Ding,Chang; Wang,Qian; Lu,Zhiping

doi:10.3892/mmr.2020.10957

Protective effect of microRNA‑381 against inflammatory damage of endothelial cells during coronary heart disease by targeting CXCR4

Authors:
- Yimin Li
- Jin Huang
- Hong Yan
- Xiangyu Li
- Chang Ding
- Qian Wang
- Zhiping Lu
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Affiliations: Department of Cardiology, Nanjing Chest Hospital, Nanjing, Jiangsu 210029, P.R. China, Inspection Center, Nanjing Chest Hospital, Nanjing, Jiangsu 210029, P.R. China
Published online on: January 22, 2020 https://doi.org/10.3892/mmr.2020.10957
Pages: 1439-1448
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Coronary heart disease (CHD) is the leading cause of human morbidity and mortality worldwide. MicroRNA (miRNA) profiling is an innovative method of identifying biomarkers for many diseases and may be a powerful tool in the diagnosis and treatment of CHD. The present study aimed to analyze the effects of miRNA (miR)‑381 on the inflammatory damage of endothelial cells during CHD. A total of 21 patients with CHD and 21 healthy control patients were enrolled in this study. Reverse transcription‑quantitative PCR, western blotting and immunofluorescence assays were conducted to examine the expression levels of miR‑381, C‑X‑C chemokine receptor type 4 (CXCR4), Bcl‑2, Bax, Cleaved‑Caspases‑3 and ‑9, p38, ERK1/2 and JNK. Cell Counting Kit‑8, EdU and flow cytometry experiments were performed to evaluate cell proliferation and apoptosis. An ELISA was adopted to determine the expressions of inflammatory factors (interleukins‑8, ‑6 and ‑1β, and tumor necrosis factor‑α). In addition, a dual‑luciferase reporter assay was used to determine the relationship between miR‑381 and CXCR4. Decreased miR‑381 expression and increased CXCR4 expression in the plasma were observed in the CHD group compared with the normal group, which indicated a negative relationship between miR‑381 and CXCR4. Overexpression of miR‑381 significantly promoted the proliferation and inhibited the apoptosis of oxidized low‑density lipoprotein (OX‑LDL)‑induced human umbilical vein endothelial cells (HUVECs) through mitogen‑activated protein kinase pathway by targeting and inhibiting CXCR4. Furthermore, overexpression of miR‑381 reduced the release of inflammatory factors in OX‑LDL‑induced HUVECs. By contrast, reduced expression of miR‑381 exerted the opposite effects, which were subsequently reversed by silencing CXCR4 expression. Results from the present study indicated that miR‑381 was a CHD‑related factor that may serve as a potential molecular target for CHD treatment.

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