Abstract
Stent implantation impairs local endothelial function and may be associated with subsequent adverse cardiovascular events. Telmisartan, an angiotensin II receptor blocker that has unique peroxisome proliferator-activated-receptor-gamma-mediated effects on cardiovascular disease, has been shown to enhance endothelial function and limit neointimal hyperplasia. This study utilized hybrid biodegradable/stent nanofibers to facilitate sustained and local delivery of telmisartan to injured arterial vessels. Telmisartan and poly(d,l)-lactide-co-glycolide (PLGA) (75:25) were dissolved in hexafluoroisopropyl alcohol and electrospun into biodegradable nanofibrous tubes which were coated onto metal stents. By releasing 20% of the loaded telmisartan in 30 days, these hybrid biodegradable/stent telmisartan-loaded nanofibers increased the migration of endothelial progenitor cells in vitro, promoted endothelialization, and reduced intimal hyperplasia. As such, this work provides insights into the use of PLGA nanofibers for treating patients with an increased risk of stent restenosis.
Highlights
Catheter-based interventional strategies represent the gold standard for revascularizing artery stenosis
PLGA is a thoroughly-characterized, biodegradable, and biocompatible copolymer with medical applications that has been widely used in drug delivery systems [20,31]
Several recent reports have suggested that telmisartan has anti-atherosclerotic effects, including improving sensitization to insulin, protection against weight gain, anti-inflammation, and the downsizing of adipocytes by PPARγ activation [36]
Summary
Catheter-based interventional strategies represent the gold standard for revascularizing artery stenosis. Balloon angioplasty or limus-eluting stent implantation result in damage to endothelial cells [1,2]. The loss of a continuous endothelial monolayer induces potentially lethal consequences such as thrombus formation and restenosis [7,8]. Delayed healing arises from several factors following percutaneous coronary intervention including device-related inflammation, endothelial dysfunction, and the development of neoatherosclerosis [9]. Telmisartan, an angiotensin II receptor blocker that is routinely used in clinical practice, can improve the function of endothelial cells, reduce responses to oxidative stress, and reduce superoxide-caused damage [10,11]. The drug promotes endotheliumdependent relaxation, improves endothelial function [12,13], ameliorates the development and progression of atherosclerosis, and increases plaque stability [14,15]
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