A novel polymer-free ciglitazone-coated vascular stent: in vivo and ex vivo analysis of stent endothelialization in a rabbit iliac artery model.
OBJECTIVE
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.
Department of Medicine 1, Division of Cardiology, University Hospital of Jena, Thuringia, Germany.
Sylvia
S
Otto
Department of Medicine 1, Division of Cardiology, University Hospital of Jena, Thuringia, Germany.
Kristin
K
Jaeger
Institute for Laboratory Animal Science and Animal Protection (IVuT), University Hospital of Jena, Thuringia, Germany.
Frank D
FD
Kolodgie
Department of Medicine 1, Division of Cardiology, University Hospital of Jena, Thuringia, Germany.
Diana
D
Muehlstaedt
Department of Medicine 1, Division of Cardiology, University Hospital of Jena, Thuringia, Germany.
Marcus
M
Franz
CV Path Institute Inc., Gaithersburg, MD, USA.
Sabine
S
Bischoff
CV Path Institute Inc., Gaithersburg, MD, USA.
Harald
H
Schubert
Department of Medicine 1, Division of Cardiology, University Hospital of Jena, Thuringia, Germany.
Hans R
HR
Figulla
Institute for Laboratory Animal Science and Animal Protection (IVuT), University Hospital of Jena, Thuringia, Germany.
Renu
R
Virmani
Department of Medicine 1, Division of Cardiology, University Hospital of Jena, Thuringia, Germany.
Tudor C
TC
Poerner
D000818:Animals; D002784:Cholesterol / Q000737:chemistry; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000378:metabolism; D007083:Iliac Artery / Q000473:pathology*; D008024:Ligands; D008670:Metals; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists*; D011108:Polymers / Q000737:chemistry*; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet; D045162:Thiazolidinediones / Q000737:chemistry*; D041623:Tomography, Optical Coherence; D014465:Ultrasonics
D008024:Ligands; D008670:Metals; D047495:PPAR gamma; D011108:Polymers; D045162:Thiazolidinediones; D002784:Cholesterol; C039671:ciglitazone
PPARg; Pathology Section; ciglitazone; drug-eluting stents; endothelium; vascular remodeling