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A novel mechanism of inhibiting in-stent restenosis with arsenic trioxide drug-eluting stent: Enhancing contractile phenotype of vascular smooth muscle cells via YAP pathway

Lookup NU author(s): Dr Ling Juan Wu, Dr Richard DanielORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2020Objective: Arsenic trioxide (ATO or As2O3) has beneficial effects on suppressing neointimal hyperplasia and restenosis, but the mechanism is still unclear. The goal of this study is to further understand the mechanism of ATO's inhibitory effect on vascular smooth muscle cells (VSMCs). Methods and results: Through in vitro cell culture and in vivo stent implanting into the carotid arteries of rabbit, a synthetic-to-contractile phenotypic transition was induced and the proliferation of VSMCs was inhibited by ATO. F-actin filaments were clustered and the elasticity modulus was increased within the phenotypic modulation of VSMCs induced by ATO in vitro. Meanwhile, Yes-associated protein (YAP) nuclear translocation was inhibited by ATO both in vivo and in vitro. It was found that ROCK inhibitor or YAP inactivator could partially mask the phenotype modulation of ATO on VSMCs. Conclusions: The interaction of YAP with the ROCK pathway through ATO seems to mediate the contractile phenotype of VSMCs. This provides an indication of the clinical therapeutic mechanism for the beneficial bioactive effect of ATO-drug eluting stent (AES) on in-stent restenosis (ISR).

Publication metadata

Author(s): Zhao Y, Zang G, Yin T, Ma X, Zhou L, Wu L, Daniel R, Wang Y, Qiu J, Wang G

Publication type: Article

Publication status: Published

Journal: Bioactive Materials

Year: 2021

Volume: 6

Issue: 2

Pages: 375-385

Print publication date: 01/02/2021

Online publication date: 04/09/2020

Acceptance date: 23/08/2020

Date deposited: 03/12/2020

ISSN (electronic): 2452-199X

Publisher: KeAi Communications Co.


DOI: 10.1016/j.bioactmat.2020.08.018


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