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  

作　　者：Yinping Zhao Guangchao Zang Tieying Yin Xiaoyi Ma Lifeng Zhou Lingjuan Wu Richard Daniel Yunbing Wang Juhui Qiu Guixue Wang 

机构地区：[1]Laboratory of Tissue and Cell Biology,Lab Teaching&Management Center,Chongqing Medical University,Chongqing,400016,China [2]Key Laboratory for Biorheological Science and Technology of Ministry of Education,State and Local Joint Engineering Laboratory for Vascular Implants,Bioengineering College of Chongqing University,Chongqing,400030,China [3]Beijing Amsinomed Medical Co.,Ltd,Beijing,100021,China [4]Medical School,Newcastle University,Newcastle Upon Tyne,NE24AX,UK [5]National Engineering Research Center for Biomaterials,Sichuan University,Chengdu,610065,China

出　　处：《Bioactive Materials》2021年第2期375-385,共11页生物活性材料（英文）

基　　金：This study was supported in part by grants from the National Natural Science Foundation of China,China(31971242,31701275);the National Science Foundation of Chongqing,China(cstc2020jcjymsxmX0189);the Chongqing Research Program of Basic Research and Frontier Technology,China(CSTC2019JCYJ-ZDXM0033);Open Fund for Key Laboratory of Biorheological Science and Technology,Ministry of Education,China(CQKLBST-2019-010);Innovation Talent Project of 2020 for Chongqing Primary and secondary School,China(CY200405);the National Key R&D Program,China(2016YFC1102305);The support from the Chongqing Engineering Laboratory in Vascular Implants,China,the Public Experiment Centre of State Bioindustrial Base(Chongqing)and the National“111 Plan”,China(B06023)are gratefully acknowledged.

摘　　要：Objective: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).

关 键 词：Arsenic trioxide(ATO) Bioactive Yes-associated protein(YAP) In-stent restenosis(ISR) 

分 类 号：R318[医药卫生—生物医学工程]