miR-1290 induces endothelial-to-mesenchymal transition and promotes vascular restenosis after angioplasty by targeting FGF2

• DOI: 10.1016/j.atherosclerosis.2024.118527
• Publication Date: 2024-07-03T20:25:22Z
• Authors: Shuning Han; Xiangyu Liu; Xueying Zhang; Huibo Ma; Wei Li; Xiaozhi Sun; Tao Yu; Yongxin Li; Mingjin Guo
• Keywords: Male; Epithelial-Mesenchymal Transition; Endothelial Cells; Rats; Rats, Sprague-Dawley; Disease Models, Animal; MicroRNAs; Gene Expression Regulation; Case-Control Studies; Human Umbilical Vein Endothelial Cells; Animals; Humans; Female; Fibroblast Growth Factor 2; Carotid Artery Injuries; Angioplasty, Balloon; Cell Proliferation; Signal Transduction

Endothelial-to-mesenchymal transition (EndMT) is an important reason for restenosis but the underlying mechanisms need to be further explored. Therefore, the purpose of this study is to screen significantly different microRNAs (miRNAs) and assess their functions and downstream pathways.This study screened several miRNAs with significant differences between human arterial segments from restenosis patients and healthy volunteers using whole transcriptome resequencing and real-time quantitative reverse transcription PCR (qRT-PCR). We explored the correlation between miR-1290 and EndMT using Western blot, qRT-PCR, Pearson correlation analysis and further functional gain and loss experiments. Subsequently, we identified the direct downstream target of miR-1290 by bioinformatics analysis, RNA pull-down, double Luciferase reporter gene and other functional experiments. Finally, rat carotid artery balloon injury model demonstrated the therapeutic potential of miR-1290 regulator.We screened 129 differentially expressed miRNAs. Among them, miR-1290 levels were significantly higher in restenosis arteries than in healthy arteries, and as expected, EndMT was functionally enhanced with miR-1290 overexpression and comparatively weakened when miR-1290 was knocked down. In addition, fibroblast growth factor-2 (FGF2) was established as the downstream target of miR-1290. Finally, we utilized an animal model and found that low miR-1290 levels could alleviate EndMT and the progression of restenosis.Our study demonstrated the strong regulatory effects of miR-1290 on EndMT, endometrial hyperplasia and restenosis, which could be useful as biomarker and therapeutic target for stent implantation in patients with arterial occlusive disease of the lower extremities.