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

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).

Corrigendum to“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”[Bioact.Mater.62(February 2021)375-385]

The authors regret the publication of incorrect fund numbers in the acknowledgment section of the article.The number“cstc2019jcyj-zdxm0033”has been updated as“cstc2019jcyj-zdxmX0028”.The corrected acknowledgment section is as follows:This study was supported in part by grants from the National Natural Science Foundation,China(31971242,31701275),the Natural Science Foundation of Chongqing,China(cstc2020jcjy-msxmX0189),the Chongqing Research Program of Basic Research and Frontier Technology,China(cstc2019jcjy-dxmX0028),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)and 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.