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CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

Endothelial Cell Recovery Between Comparator Polymer-Based Drug-Eluting Stents

Michael Joner, MD^_*, Gaku Nakazawa, MD, Aloke V. Finn, MD, Shawn Chin Quee, MS, Leslie Coleman, DVM, Eduardo Acampado, DVM, Patricia S. Wilson, BA, Kristi Skorija, BS, Qi Cheng, MD, Xin Xu, PhD, Herman K. Gold, MD^||, Frank D. Kolodgie, PhD and Renu Virmani, MD, FACC^,¶,_*

^_* German Heart Center, Munich, Germany
CVPath Institute, Inc., Gaithersburg, Maryland
Cardiology Division, Emory University, Atlanta, Georgia
Abbott Vascular, Santa Clara, California
^|| Cardiac Unit, Department of Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts
^¶ Jack H. Skirball Center for Cardiovascular Research, Orangeburg, New York.

Manuscript received July 2, 2007; revised manuscript received April 23, 2008, accepted April 29, 2008.

^_* Reprint requests and correspondence: Dr. Renu Virmani, CVPath, Institute, Inc., 19 Firstfield Road, Gaithersburg, Maryland 20878. (Email: rvirmani{at}cvpath.org).

Objectives: 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 (30%) relative to EES and ML Vision controls (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.

Key Words: drug-eluting stents • endothelium • platelet-endothelial adhesion molecule-1 • vascular endothelial growth factor

Abbreviations and Acronyms   DES = drug-eluting stent(s)   EES = everolimus-eluting stent(s)   FDA = Food and Drug Administration   PECAM = platelet-endothelial cell adhesion molecule   PES = paclitaxel-eluting stent(s)   SEM = scanning electron microscopy   SES = sirolimus-eluting stent(s)   TM = thrombomodulin   VEGF = vascular endothelial growth factor   ZES = zotarolimus-eluting stent(s)

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J. Am. Coll. Cardiol. 2008 52: A33-A34. [Full Text] [PDF]