Cucurbitacins mitigate vascular neointimal hyperplasia by suppressing cyclin A2 expression and inhibiting VSMC proliferation

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外文摘要：Background:Restenosis frequently occurs after percutaneous angioplasty in patients with vascular occlusion and seriously threatens their health.Substantial evidence has revealed that preventing vascular smooth muscle cell proliferation using a drug-eluting stent is an effective approach to improve restenosis.Cucurbitacins have been demonstrated to exert an anti-proliferation effect in various tumors and a hypoten-sive effect.This study aims to investigate the role of cucurbitacins extracted from Cucumis melo L.(CuECs) and cucurbitacin B (CuB) on restenosis.Methods:C57BL/6 mice were subjected to left carotid artery ligation and subcu-taneously injected with CuECs or CuB for 4 weeks.Hematoxylin-Eosin,immuno-fluorescence and immunohistochemistry staining were used to evaluate the effect of CuECs and CuB on neointimal hyperplasia.Western blot,real-time PCR,flow cytometry analysis,EdU staining and cellular immunofluorescence assay were em-ployed to measure the effects of CuECs and CuB on cell proliferation and the cell cycle in vitro.The potential interactions of CuECs with cyclin A2 were performed by molecular docking.Results:The results demonstrated that both CuECs and CuB exhibited significant inhibitory effects on neointimal hyperplasia and proliferation of vascular smooth muscle cells.Furthermore,CuECs and CuB mediated cell cycle arrest at the S phase.Autodocking analysis demonstrated that CuB,CuD,CuE and CuI had high binding en-ergy for cyclin A2.Our study also showed that CuECs and CuB dramatically inhibited FBS-induced cyclin A2 expression.Moreover,the expression of cyclin A2 in CuEC-and CuB-treated neointima was downregulated.Conclusions:CuECs,especially CuB,exert an anti-proliferation effect in VSMCs and may be potential drugs to prevent restenosis.

外文关键词：

CuBCucurbitacincyclin A2restenosisvascular smooth muscle cell

作者：

Ruqiang Yuan、Lei Qian、Hu Xu、Weijing Yun

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作者单位：

Advanced Institute for Medical Sciences,Dalian Medical University,Dalian,China

Health Science Center,East China Normal University,Shanghai,China

基金：

Scientific Research Fund Project of Liaoning Provincial Department of EducationScientific Research Fund Project of Liaoning Provincial Department of EducationScientific Research Fund Project of Liaoning Provincial Department of EducationNational Natural Science Foundation of China Grants

项目编号：

LJKMZ20221267LJKZ0840LJKZ084781900267

出版年：

2024

DOI：

10.1002/ame2.12457

动物模型与实验医学(英文)

中国实验动物学会,中国医学科学院医学实验动物研究所

动物模型与实验医学(英文)

ISSN：2096-5451

年,卷(期)：2024.7(4)