Zedoarondiol Inhibits Neovascularization in Atherosclerotic Plaques of ApoE-/- Mice by Reducing Platelet Exosomes-Derived MiR-let-7a.
10.1007/s11655-024-4003-2
- Author:
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
;
Fu-Hai ZHAO
4
,
5
Author Information
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. Cardiovascular Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. 13911134962@
5. com.
- Publication Type:Journal Article
- Keywords:
atherosclerosis;
exosomes;
miR-let-7a;
neovascularization;
thrombospondin 1;
zedoarondiol
- MeSH:
Animals;
MicroRNAs/genetics*;
Exosomes/drug effects*;
Plaque, Atherosclerotic/genetics*;
Neovascularization, Pathologic/genetics*;
Human Umbilical Vein Endothelial Cells/metabolism*;
Humans;
Blood Platelets/drug effects*;
Apolipoproteins E/deficiency*;
Thrombospondin 1/metabolism*;
CD36 Antigens/metabolism*;
Platelet Activation/drug effects*;
Male;
Mice;
Mice, Inbred C57BL
- From:
Chinese journal of integrative medicine
2025;31(3):228-239
- CountryChina
- Language:English
-
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.
