A novel polymer-free ciglitazone-coated vascular stent: in vivo and ex vivo analysis of stent endothelialization in a rabbit iliac artery model

Autor: Sylvia Otto, Tudor C. Poerner, Kristin Jaeger, Marcus Franz, Harald Schubert, Frank D. Kolodgie, Hans R. Figulla, Diana Muehlstaedt, Renu Virmani, Sabine Bischoff
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: // Sylvia Otto 1 , Kristin Jaeger 1 , Frank D. Kolodgie 2 , Diana Muehlstaedt 1 , Marcus Franz 1 , Sabine Bischoff 3 , Harald Schubert 3 , Hans R. Figulla 1 , Renu Virmani 2 and Tudor C. Poerner 1 1 Department of Medicine 1, Division of Cardiology, University Hospital of Jena, Thuringia, Germany 2 Institute for Laboratory Animal Science and Animal Protection (IVuT), University Hospital of Jena, Thuringia, Germany 3 CV Path Institute Inc., Gaithersburg, MD, USA Correspondence to: Sylvia Otto, email: // Keywords : PPARg, ciglitazone, endothelium, vascular remodeling, drug-eluting stents, Pathology Section Received : July 16, 2016 Accepted : August 20, 2016 Published : August 24, 2016 Abstract Aim: Peroxisome proliferator-activated receptor-gamma (PPARg) agonists have known pleiotropic cardiovascular effects with favourable properties in vascular remodeling, and specifically in suppression of vascular smooth muscle cell proliferation. A novel vascular stent coating using the PPARg ligand ciglitazone (CCS) was investigated regarding its effects on endothelialization after 7 and 28 days. Methods: Microporous bare metal stents (BMS) were coated with ciglitazone by ultrasonic flux with a load of 255 μg ciglitazone/stent. SixteenNew Zealand white rabbits, fed a with high cholesterol diet, underwent stent implantation in both iliac arteries. Everolimus-eluting stents (EES) and BMS were comparators. Histology (CD 31 immunostaining, confocal and scanning electron microscopy, morphometry) was performed after 7 and 28 days and by OCT (optical coherence tomography) in vivo after 28 days. Results: Microscopy showed comparable results with near complete endothelialization in CCS and BMS (%CD31 above stent struts after 7 days: 67.92±36.35 vs. 84.48±23.86; p = 0.55; endothel % above stent struts: 77.22±27.9 vs. 83.89±27.91; p = 0.78). EES were less endothelialized with minimal fibrin deposition, not found in BMS and CCS (% CD 31 above struts after 28 days, BMS: 100.0±0.0 vs. EES: 95.9±3.57 vs. CCS: 100.0±0.0; p = 0.0292). OCT revealed no uncovered struts in all stents after 28 days. Conclusions: Polymer-free coating with ciglitazone, a PPARg agonist is feasible and stable over time. Our data prove unimpaired endothelial coverage of a ciglitazone-coated vascular stent system by histology and OCT. Thus, this PPARg agonist coating deserves further investigation to evaluate its potency on local neointimal suppression.
Databáze: OpenAIRE