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. 2025 Mar;31(3):228-239.
doi: 10.1007/s11655-024-4003-2. Epub 2024 Dec 6.

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

Bei-Li Xie  1 , Bo-Ce Song  2 , Ming-Wang Liu  1 , Wei Wen  1 , Yu-Xin Yan  1 , Meng-Jie Gao  3 , Lu-Lian Jiang  3 , Zhi-Die Jin  1 , Lin Yang  1 , Jian-Gang Liu  1 , Da-Zhuo Shi  1   4 , Fu-Hai Zhao  5   6
Affiliations

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

Bei-Li Xie et al. Chin J Integr Med. 2025 Mar.

Abstract

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.

Keywords: atherosclerosis; exosomes; miR-let-7a; neovascularization; thrombospondin 1; zedoarondiol.

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Conflict of interest statement

Conflict of Interest: No conflict of interest declared. Declaration of Figures Authenticity: All figures submitted have been created by the authors who confirm that the images are original with no duplication and have not been previously published in whole or in part.

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