Joner Michael, Nakazawa Gaku, Finn Aloke V, Quee Shawn Chin, Coleman Leslie, Acampado Eduardo, Wilson Patricia S, Skorija Kristi, Cheng Qi, Xu Xin, Gold Herman K, Kolodgie Frank D, Virmani Renu
German Heart Center, Munich, Germany.
J Am Coll Cardiol. 2008 Jul 29;52(5):333-42. doi: 10.1016/j.jacc.2008.04.030.
The purpose of this study was to assess trends in endothelial coverage and recovery among leading polymer-based drug-eluting stents (DES).
Autopsy studies of human U.S. Food and Drug Administration (FDA)-approved DES implanted coronary arteries suggest that complications of late stent thrombosis are associated with incomplete endothelial coverage of struts.
Rabbits received sirolimus-eluting stents (SES), paclitaxel-eluting stents (PES), zotarolimus-eluting stents (ZES), and everolimus-eluting stents (EES) for 14 or 28 days along with MULTI-LINK (ML) Vision control stents. Endothelial coverage above and between struts was measured by morphometric analysis of images acquired through en face scanning electron microscopy. Dual fluorescent immunolabeling was performed for platelet-endothelial cell adhesion molecule (PECAM)-1 and thrombomodulin (TM), factors involved in cell-to-cell contact and thrombogenicity, respectively. In a separate analysis, the endothelial mitogen, vascular endothelial growth factor (VEGF), was also assessed.
Varying rates of endothelialization among comparator DES were most notable at 14 days, where coverage above struts remained poor in SES, PES, and ZES (<or=30%) relative to EES and ML Vision controls (>or=70%), whereas no significant differences were observed at 28 days. Select DES with poor endothelialization showed a further reduced expression of PECAM-1. All DES showed an absence or weak expression of the antithrombotic cofactor TM. Incomplete endothelialization in select DES was further associated with increased VEGF secretion and messenger ribonucleic acid levels at 14 days, providing evidence of a transitional healing surface.
The present study marks the first comparator analysis of endothelial coverage in leading polymeric DES, supporting disparities in arterial healing based on endothelial regrowth and recovery, favoring newer designs over the current generation of FDA-approved stents.
本研究旨在评估主要聚合物基药物洗脱支架（DES）的内皮覆盖及恢复趋势。
对美国食品药品监督管理局（FDA）批准的植入冠状动脉的DES进行尸检研究表明，晚期支架血栓形成并发症与支架小梁内皮覆盖不完全有关。
给兔子植入西罗莫司洗脱支架（SES）、紫杉醇洗脱支架（PES）、佐他莫司洗脱支架（ZES）和依维莫司洗脱支架（EES）14天或28天，同时植入MULTI-LINK（ML）Vision对照支架。通过对经正面扫描电子显微镜获取的图像进行形态计量分析，测量支架小梁上方及之间的内皮覆盖情况。分别对血小板内皮细胞黏附分子（PECAM）-1和血栓调节蛋白（TM）进行双重荧光免疫标记，这两种因子分别参与细胞间接触和血栓形成。在另一项分析中，还评估了内皮有丝分裂原血管内皮生长因子（VEGF）。
在14天时，各对照DES的内皮化速率差异最为显著，SES、PES和ZES支架小梁上方的覆盖情况相对于EES和ML Vision对照支架（≥70%）仍然较差（≤30%），而在28天时未观察到显著差异。内皮化较差的特定DES显示PECAM-1表达进一步降低。所有DES均显示抗血栓辅因子TM缺乏或表达较弱。特定DES的内皮化不完全还与14天时VEGF分泌增加和信使核糖核酸水平升高有关，这为过渡性愈合表面提供了证据。
本研究是对主要聚合物DES内皮覆盖的首次对照分析，支持基于内皮再生长和恢复的动脉愈合差异，表明新一代设计优于当前FDA批准的支架。
