Objective:

2

To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment.

Methods:

2

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:

2

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 incre

ased the tube length of cells

while reducing the expressions of THBS-1 and CD36.

Conclusion:

2

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.