title: Endothelial cell recovery between comparator polymer-based drug-eluting stents.
abstract: OBJECTIVE
  The purpose of this study was to assess trends in endothelial coverage and recovery among leading polymer-based drug-eluting stents (DES).
  
  
  BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: German Heart Center, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Joner
authors.forename: Gaku
authors.initials: G
authors.lastname: Nakazawa
authors.forename: Aloke V
authors.initials: AV
authors.lastname: Finn
authors.forename: Shawn Chin
authors.initials: SC
authors.lastname: Quee
authors.forename: Leslie
authors.initials: L
authors.lastname: Coleman
authors.forename: Eduardo
authors.initials: E
authors.lastname: Acampado
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Wilson
authors.forename: Kristi
authors.initials: K
authors.lastname: Skorija
authors.forename: Qi
authors.initials: Q
authors.lastname: Cheng
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Herman K
authors.initials: HK
authors.lastname: Gold
authors.forename: Frank D
authors.initials: FD
authors.lastname: Kolodgie
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D054855:Drug-Eluting Stents; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D000068338:Everolimus; D008855:Microscopy, Electron, Scanning; D023421:Models, Animal; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011108:Polymers; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D018180:Thrombomodulin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011108:Polymers; D012333:RNA, Messenger; D018180:Thrombomodulin; D042461:Vascular Endothelial Growth Factor A; D000068338:Everolimus; C489443:zotarolimus; D017239:Paclitaxel; D020123:Sirolimus