Otto Sylvia, Jaeger Kristin, Kolodgie Frank D, Muehlstaedt Diana, Franz Marcus, Bischoff Sabine, Schubert Harald, Figulla Hans R, Virmani Renu, Poerner Tudor C
Department of Medicine 1, Division of Cardiology, University Hospital of Jena, Thuringia, Germany.
Institute for Laboratory Animal Science and Animal Protection (IVuT), University Hospital of Jena, Thuringia, Germany.
Oncotarget. 2016 Sep 6;7(36):57571-57580. doi: 10.18632/oncotarget.11584.
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.
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.
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.
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.
过氧化物酶体增殖物激活受体γ（PPARγ）激动剂具有多效性心血管效应，在血管重塑尤其是抑制血管平滑肌细胞增殖方面具有有利特性。研究了一种使用PPARγ配体吡格列酮（CCS）的新型血管支架涂层在7天和28天后对内皮化的影响。
用超声通量法将吡格列酮以255μg/支架的负载量涂覆在微孔裸金属支架（BMS）上。16只喂食高胆固醇饮食的新西兰白兔在双侧髂动脉植入支架。依维莫司洗脱支架（EES）和BMS作为对照。在7天和28天后进行组织学检查（CD 31免疫染色、共聚焦和扫描电子显微镜、形态测量），并在28天后通过光学相干断层扫描（OCT）进行体内检查。
显微镜检查显示CCS和BMS的结果相当，内皮化接近完全（7天后支架支柱上方CD31百分比：67.92±36.35对84.48±23.86；p = 0.55；支架支柱上方内皮百分比：77.22±27.9对83.89±27.91；p = 0.78）。EES的内皮化程度较低，纤维蛋白沉积最少，在BMS和CCS中未发现（28天后支柱上方CD 31百分比，BMS：100.0±0.0对EES：95.9±3.57对CCS：100.0±0.0；p = 0.029）。28天后OCT显示所有支架均无未覆盖的支柱。
用PPARγ激动剂吡格列酮进行无聚合物涂层是可行的，且随时间稳定。我们的数据通过组织学和OCT证明吡格列酮涂层血管支架系统的内皮覆盖未受损害。因此，这种PPARγ激动剂涂层值得进一步研究以评估其对局部新生内膜抑制的效力。
