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.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32954055.
- Also identified by DOI 10.1016/j.bioactmat.2020.08.018 and PMC identifier 7484501.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Arsenic trioxide (ATO or As<sub>2</sub>O<sub>3</sub>) 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). Through <i>in vitro</i> cell culture and <i>in vivo</i> 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 <i>in vitro</i>. Meanwhile, Yes-associated protein (YAP) nuclear translocation was inhibited by ATO both <i>in vivo</i> and <i>in vitro</i>. It was found that ROCK inhibitor or YAP inactivator could partially mask the phenotype modulation of ATO on VSMCs. 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).