Arsenic Trioxide–Coated Stent Is an Endothelium‐Friendly Drug Eluting Stent

Abstract

An ideal vascular stent would both inhibit in-stent restenosis (ISR) and promote rapid re-endothelialization. In the current study, the performance of arsenic trioxide (ATO)-drug eluting stent (AES) is compared with the bare metal stent, poly-lactic-co-glycolic acid-coating metal stent, and rapamycin-drug eluting stent (RES). In vivo AES is shown to prevent neointimal hyperplasia more efficiently than the others when implanted into the carotid arteries of rabbits. Moreover, AES promotes endothelial cells proliferation and re-endothelialization more quickly than RES. In vitro ATO exposure significantly increases the viability, proliferation, adhesion, and spreading of primary porcine coronary artery endothelial cells (PCAECs), which are critical for endothelialization. However, ATO exposure reduces the viability of porcine coronary artery smooth muscle cells (PCASMCs). The evaluation of mitochondrial morphology, membrane potential, and function demonstrates that ATO at 2 µmol L causes enlargement of the mitochondrion, enhancement of mitochondrial membrane potential, and adenosine triphosphate (ATP) production in PCAECs but not in PCASMCs. Thus, both in vivo and in vitro studies demonstrate that AES is an effective strategy for rapid re-endothelialization and inhibition of ISR.

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

“…The rabbits were randomly divided into three groups, i.e., BMS, PMS, and AES, and the analysis was repeat 3 times. The implantation of stents into New Zealand male rabbits was performed as described previously [ 10 ].…”

“…ATO has also shown efficacy against other tumors largely due to its anti-proliferative or pro-apoptotic properties [ 7 ], and because of this anti-proliferative effect, ATO was introduced into the field of drug-eluting stents (DES) [ 8 , 9 ]. Our previous data proved that ATO-drug eluting stent (AES) has the capacity to both promote rapid re-endothelialization and inhibit in-stent restenosis (ISR) in the responding concentration of ATO [ 10 ], but the mechanisms by which ATO inhibits ISR are largely unknown.…”

“…In response to environmental stimuli, such as injury or stent implantation, VSMCs can go through dramatic phenotypic transitions from a differentiated (‘contractile’) phenotype to a dedifferentiated (‘synthetic’) phenotype [ 12 ] exhibiting different function and morphology phenotypes [ 13 ]. It is well established that the synthetic phenotype of VSMCs is the cause of vascular proliferation remodeling diseases such as hypertension [ 14 ], atherosclerosis [ 15 ], intimal hyperplasia and ISR [ 10 , 16 , 17 ]. Therefore, the effective regulation of VSMCs phenotype modulation is crucial for the treatment of cardiovascular diseases and regeneration.…”

Surface Engineering of Cardiovascular Devices for Improved Hemocompatibility and Rapid Endothelialization

“…Results demonstrated enhanced hemocompatibility and vascular regeneration, and reduced inflammatory responses and intimal hyperplasia. Besides, other antithrombosis drugs (e.g., dipyridamole [165] and arsenic trioxide [166] ), some anticancer drugs (e.g., elemene [167] ) and lipid-lowering drugs (e.g., atorvastatin and fenofibrate [168] ) have also been utilized to improve the biological functions of tissue-engineering grafts. The efficient drug release from polymeric substrates or metal stents could not only significantly reduce platelets attachment and aggregation, but also accelerate endothelialization by inhibiting SMC proliferation.…”

Atherosclerosis Treatment with Stimuli‐Responsive Nanoagents: Recent Advances and Future Perspectives

“…However, the delayed re‐endothelialization, inflammation, and hypersensitivity of DESs can induce late ST, thereby raising the long‐term safety concern . To tackle this problem, elemene, arsenic trioxide, docetaxel, and rapamycin (RAP) have been utilized as drug candidates in DESs; multiple layer coatings using platelet glycoprotein IIb/IIIa receptor antibody SZ‐21 and poly‐ l ‐lactic acid (PLLA) can suppress ISR, promote rapid re‐endothelialization, and inhibit VSMC proliferation . In addition, biodegradable polymers are now being tested as the stent material .…”