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ox-LDL regulates proliferation and apoptosis in VSMCs by controlling the miR-183-5p/FOXO1

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Abstract

Background

microRNA–mRNA axes that are involved in oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs) proliferation/apoptosis imbalance need to be further investigated.

Objective

To investigate the functional role of miR-183-5p/FOXO1 in VSMCs and its interaction with ox-LDL.

Methods

RNA sequencing was used to detect transcriptome changes of VSMCs treated with ox-LDL. miR-183-5p and FOXO1 expression levels in VSMCs after ox-LDL treatment were assessed using qRT-PCR and western blotting. The regulatory effect of miR-183-5p on FOXO1 has been tried to prove using a dual-luciferase reporter assay. The functions of miR-183-5p, and FOXO1 were analyzed by CCK-8 assay and flow cytometry assay. The tissue samples or serum samples of high fat-feeding mice and carotid atherosclerosis patients were collected, and the levels of miR-183-5p/FOXO1 were analyzed.

Results

RNA sequencing data showed 81 miRNAs including miR-183-5p was significantly changed after ox-LDL treatment in VSMCs. FOXO1, a miR-183-5p’s potential target, was also down-regulated in ox-LDL treated cells. qRT-PCR and western blot found that expression of FOXO1 mRNA and protein significantly reduced in VSMCs treated with ox-LDL, accompanied by overexpression of miR-183-5p. miR-183-5p inhibited FOXO1 mRNA by binding to its 3’ UTR. Interference miR-183-5p/FOXO1 could change proliferation/apoptosis imbalance in VSMCs under ox-LDL stimulation. Higher levels of miR-183-5p but reduced FOXO1 can be found in the thoracic aorta tissues of high fat-feeding mice. In serum samples from individuals with carotid atherosclerosis, Higher levels of miR-183-5p were observed. the miR-183-5p level was positively related to the level of serum ox-LDL in patients.

Conclusions

Aberrant expression of miR-183-5p/FOXO1 pathway mediated ox-LDL-induced proliferation/apoptosis imbalance in VSMCs. The miR-183-5p/FOXO1 axis can potentially be utilized as the target in the treatment of patients with atherosclerosis.

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Acknowledgements

The study was supported by the fellowship of China Postdoctoral Science Foundation (Nr.:2020M681559), Key Project supported by Medical Science and technology development Foundation, Nanjing Department of Health (YKK20088), and Key Project supported by Medical Science and technology development Foundation, Nanjing Department of Health (ZKX20026).

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    Authors and Affiliations

    1. Department of Cardiology, Affiliated Hospital of Gansu Medical College, Kongtong Avenue (East Section), 744000, Pingliang, Gansu Province, China

      Mingqiang Fan, Xiangxiang Yang, Jing Bai, Qiaoke Si, Zhengfei Peng & Ding Tao

    2. Department of Chinese Medicine Management, Affiliated Hospital of Gansu Medical College, 744000, Pingliang, China

      Yinglong Huang

    3. Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 210008, Nanjing, China

      Kunsheng Li

    4. Department of Cardiology, Zhongshan Hospital, Xiamen University, 361004, Xiamen, China

      Chunwen Jia

    5. Department of Hepatobiliary and Pancreas Surgery, The Second Clinical Medical College, (Shenzhen People’s Hospital), Jinan University, 518020, Shenzhen, Guangdong, China

      Qiangnu Zhang

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    1. Mingqiang Fan
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    Contributions

    Conceiving and designing the study: FMQ, DT, LKS, HYL; Collecting the data: FMQ, HYL, YXX, LKS, SQK, PZF, CWJ; Analyzing and interpreting the data: FMQ, ZQN, YXX, CWJ; Writing the manuscript: FMQ, LKS, HYL, ZQN; Obtaining funding: DT, LKS, BY.

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    Correspondence to Ding Tao.

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    Mingqiang Fan, Yinglong Huang, Kunsheng Li, Xiangxiang Yang, Jing Bai, Qiaoke Si1, Zhengfei Peng, Chunwen Jia, Qiangnu Zhang, and Ding Tao declare that they have no conflict of interest.

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    Fan, M., Huang, Y., Li, K. et al. ox-LDL regulates proliferation and apoptosis in VSMCs by controlling the miR-183-5p/FOXO1. Genes Genom 44, 671–681 (2022). https://doi.org/10.1007/s13258-022-01236-x

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