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

Abstract

Objective Arsenic trioxide (ATO or As 2 O 3 ) 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).

Two-stage degradation and novel functional endothelium characteristics of a 3-D printed bioresorbable scaffold

“…For instance, drugs with different therapeutic effects can be combined to meet the requirements of staged vascular repair. Anti-inflammatory, anti-proliferative, anti-thrombotic, and intimal function-promoting drug coatings can be applied during the 0–6 months [ 37 , 59 , 60 ], whereas the drug coatings promoting the positive phenotype of media cells and extracellular matrix repair can be applied after 6 months. The design of a coaxial drug coating, as previously reported by us, provides a means to achieve the staged release of drugs with different efficiencies [ 61 ].…”

Bioimpedance Sensing of Implanted Stent Occlusions: Smart Stent

“…It will be necessary to study the implementation of the power supply for the intelligent stent, its integration and its fabrication in reduced dimensions and biocompatible materials. It will also be essential to study the clinical security, the placement of the integrated circuits in appropriated biological sites in order not to create additional stenosis problems due to the electronic components, in line with the general tendency of minimizing invasiveness [ 6 ]. Biocompatibility of the materials used is also essential, as other materials will be needed for the electronic development of the impedance measurement system, apart from traditional stent materials (cobalt chromium, 316 L stainless steel).…”

“…The use of drug-eluting stents has important implications for the care of individual patients and the delivery and economics of health care in general [ 5 ]. Different drugs are being tested as a potential therapeutic approach for ameliorating vascular occlusive diseases [ 6 ]. Diabetes, multiple stents, and smaller final minimal lumen diameter (MLD) are strong predictors of restenosis after coronary stent placement [ 7 ].…”

Challenges and strategies for in situ endothelialization and long-term lumen patency of vascular grafts

“…IH has high incidence in causing long-term vascular occlusion several months after implantation, which is caused by uncontrollable SMC pathological proliferation [ 234 ].ECs, serving as the paramount defender in vascularization, can release molecules for IH inhibition. Apart from promoting EC adhesion and activation, some drugs like E2F and MK2i also have potential in preventing IH by controlling SMC proliferation in a more direct way [ 235 ]. In clinic, E2F transcription factor was utilized to keep a 30 min lumen patency for the vascular tissue in vitro .…”