Oncotarget

Research Papers: Pathology:

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

Sylvia Otto _, Kristin Jaeger, Frank D. Kolodgie, Diana Muehlstaedt, Marcus Franz, Sabine Bischoff, Harald Schubert, Hans R. Figulla, Renu Virmani and Tudor C. Poerner

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Oncotarget. 2016; 7:57571-57580. https://doi.org/10.18632/oncotarget.11584

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Abstract

Sylvia Otto1, Kristin Jaeger1, Frank D. Kolodgie2, Diana Muehlstaedt1, Marcus Franz1, Sabine Bischoff3, Harald Schubert3, Hans R. Figulla1, Renu Virmani2 and Tudor C. Poerner1

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.


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