Endothelial cell recovery between comparator polymer-based drug-eluting stents.
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.
Joner
Michael
M
German Heart Center, Munich, Germany.
Nakazawa
Gaku
G
Finn
Aloke V
AV
Quee
Shawn Chin
SC
Coleman
Leslie
L
Acampado
Eduardo
E
Wilson
Patricia S
PS
Skorija
Kristi
K
Cheng
Qi
Q
Xu
Xin
X
Gold
Herman K
HK
Kolodgie
Frank D
FD
Virmani
Renu
R
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
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