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
Cardiovascular Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Cardiovascular Department, Beijing Hospital of Integrated Chinese and Western Medicine, Beijing, 100091, China.
Chin J Integr Med. 2025 Mar;31(3):228-239. doi: 10.1007/s11655-024-4003-2. Epub 2024 Dec 6.
To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment.
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.
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.
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.
通过外泌体实验研究莪术二醇对动脉粥样硬化（AS）斑块新生血管形成的影响。
将载脂蛋白E（ApoE）小鼠喂以高脂饮食以建立AS模型，并分别用高剂量和低剂量（每日10、5 mg/kg）的莪术二醇进行治疗。14周后，检测斑块中抗血管生成蛋白血小板反应蛋白1（THBS-1）及其受体CD36的表达，以及血小板活化率和外泌体来源的微小RNA-let-7a。然后，用莪术二醇在体外干预血小板，并检测血小板衍生外泌体（Pexo）中的miR-let-7a。最后，用miR-let-7a模拟物转染人脐静脉内皮细胞（HUVECs）并用Pexo处理，以观察Pexo中miR-let-7a对血管形成的影响。
动物实验表明，用莪术二醇治疗后，AS小鼠斑块中的新生血管密度显著降低，THBS-1和CD36增加，血小板活化率明显降低，Pexo中的miR-let-7a水平降低（P<0.01）。体外实验中，莪术二醇干预后Pexo中的血小板活化率和miR-let-7a水平显著降低。细胞实验表明，Pexo干预后，血管长度增加，miR-let-7a模拟物的转染进一步增加了细胞的血管长度，同时降低了THBS-1和CD36的表达。
莪术二醇具有抑制AS小鼠斑块内新生血管形成的作用，其机制可能与抑制血小板活化和降低Pexo衍生的微小RNA-let-7a水平有关。
