Is it time for a retinoic acid-eluting stent or retinoic acid-coated balloon? Insights from experimental studies of systemic and local delivery of retinoids.

Although the incidence of restenosis and stent thrombosis has substantially declined during the last decades, they still constitute the two major causes of stent failure. These complications are partially attributed to the currently used cytostatic drugs, which can cause local inflammation, delay or prevent re-endothelialization and essentially cause arterial cell toxicity. Retinoic acid (RA), a vitamin A (retinol) derivative, is a naturally occurring substance used for the treatment of cell proliferation disorders. The agent has pleiotropic effects on vascular smooth muscle cells and macrophages: it influences the proliferation, migration, and transition of smooth muscle cells to other cell types and modulates macrophage activation. These observations are supported by accumulated evidence from in vitro and in vivo experiments. In addition, systemic and topical administration of RA can decrease the development of atherosclerotic plaques and reduce or inhibit restenosis after vascular injury (caused by embolectomy, balloon catheters, or ligation of arteries) in various experimental models. Recently, an RA-drug eluting stent (DES) has been tested in an animal model. In this review, we explore the effects of RA in atherosclerosis and the potential of the local delivery of RA through an RA-DES or RA-coated balloon for targeted therapeutic percutaneous vascular interventions. Despite promising published results, further experimental study is warranted to examine the safety and efficacy of RA-eluting devices in vascular artery disease.

Histopathological evaluation of a retinoic acid eluting stent in a rabbit iliac artery model.

This study aimed to evaluate the safety and efficacy of innovative retinoic acid (RA) eluting stents with bioabsorbable polymer. Sixty stents divided in ten groups were implanted in the iliac arteries of 30 rabbits. Two polymers ("A", poly (lactic-co-glycolic acid) and "B", polylactic acid), and three doses ("Low", "Medium" and "High") of RA (groups: AL, AM, AH, BL, BM, BH) were used on cobalt chromium stents (Rontis Corporation), one group of bare stent (C), one group (D) of Everolimus eluting stent (Xience-Pro, Abbot Vascular), and two groups of Rontis Everolimus eluting stents coated with polymer A (EA) and B (EB). Treated arteries were explanted after 4 weeks, processed by methyl methacrylate resin and evaluated by histopathology. None of the implanted stents was related with thrombus formation or extensive inflammation. Image analysis showed limited differences between groups regarding area stenosis (BH, D and EB groups had the lower values). Group BH had lower intimal mean thickness than AH (105.1 vs 75.3 µm, p = 0.024). Stents eluting RA, a non-cytotoxic drug, were not related with thrombus formation and had an acceptable degree of stenosis 4 weeks post implantation. RA dose and type of polymer may play role in the biocompatibility of the stents.