Zedoarondiol Inhibits Neovascularization in Atherosclerotic Plaques of ApoE^(-/-)Mice by Reducing Platelet Exosomes-Derived MiR-let-7a  

作　　者：XIE Bei-li SONG Bo-ce LIU Ming-wang WEN Wei YAN Yu-xin GAO Meng-jie JIANG Lu-lian JIN Zhi-die YANG Lin LIU Jian-gang SHI Da-zhuo ZHAO Fu-hai 

机构地区：[1]Cardiovascular Department,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing,100091,China [2]Cardiovascular Department,Beijing Hospital of Integrated Chinese and Western Medicine,Beijing,100091,China [3]Graduate School of Beijing University of Chinese Medicine,Beijing,100091,China [4]National Clinical Research Center for Chinese Medicine Cardiology,Beijing,100091,China

出　　处：《Chinese Journal of Integrative Medicine》2025年第3期228-239,共12页中国结合医学杂志(英文版)

基　　金：Supported by the Science and Technology Innovation Project of Chinese Academy of Traditional Chinese Medicine(No.CI2021A00910);the National Natural Science Foundation of China(No.81973674)。

摘　　要：Objective:To investigate the effect of zedoarondiol on neovascularization of atherosclerotic(AS)plaque by exosomes experiment.Methods:ApoE^(-/-)mice were fed with high-fat diet to establish AS model and treated with high-and low-dose(10,5 mg/kg daily)of zedoarondiol,respectively.After 14 weeks,the expressions of anti-angiogenic protein thrombospondin 1(THBS-1)and its receptor CD36 in plaques,as well as platelet activation rate and exosome-derived miR-let-7a were detected.Then,zedoarondiol was used to intervene in platelets in vitro,and miR-let-7a was detected in platelet-derived exosomes(Pexo).Finally,human umbilical vein endothelial cells(HUVECs)were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation.Results:Animal experiments showed that after treating with zedoarondiol,the neovascularization density in plaques of AS mice was significantly reduced,THBS-1 and CD36 increased,the platelet activation rate was markedly reduced,and the miR-let-7a level in Pexo was reduced(P<0.01).In vitro experiments,the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention.Cell experiments showed that after Pexo's intervention,the tube length increased,and the transfection of miR-let-7a minics further increased the tube length of cells,while reducing the expressions of THBS-1 and CD36.Conclusion:Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice,and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.

关 键 词：zedoarondiol atherosclerosis NEOVASCULARIZATION thrombospondin 1 EXOSOMES miR-let-7a 

分 类 号：R285.5[医药卫生—中药学]