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Anti-CD34 Antibodies Immobilized on the Surface of Sirolimus-Eluting Stents Enhance Stent Endothelialization

Gaku Nakazawa, MD^_*, Juan F. Granada, MD, Carlos L. Alviar, MD, Armando Tellez, MD, Greg L. Kaluza, MD, PhD, Margaret Yoklavich Guilhermier, BS, Sherry Parker, PhD, Stephen M. Rowland, PhD, Frank D. Kolodgie, PhD^_*, Martin B. Leon, MD, Renu Virmani, MD^_*,_*

^_* CVPath Institute, Inc., Gaithersburg, Maryland
Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, New York, New York
OrbusNeich Medical, Fort Lauderdale, Florida
Cardiovascular Research Foundation, New York, New York

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

Objectives: In this study, we hypothesized that an antihuman-CD34 antibody immobilized on the surface of commercially available sirolimus-eluting stents (SES) could enhance re-endothelialization compared with SES alone.

Background: Previous experience with antihuman-CD34 antibody surface modified Genous stents (GS) (OrbusNeich Medical, Fort Lauderdale, Florida) has shown enhanced stent endothelialization in vivo.

Methods: In the phase 1 study, stents were deployed in 21 pig coronary arteries for single stenting (9 vessels: 3 GS, 3 SES, and 3 bare-metal stents) and overlapping stenting with various combinations (12 vessels: 4 GS+GS, 4 SES+SES, and 4 GS+SES) and harvested at 14 days for scanning electron and confocal microscopy. In phase 2, immobilized anti-CD34 antibody coating was applied on commercially available SES (SES–anti-CD34, n = 7) and compared with GS (n = 8) and SES (n = 7) and examined at 3 and 14 days by scanning electron/confocal microscopy analysis.

Results: In phase 1, single stent implantation showed greatest endothelialization in GS (99%) and in bare-metal stent (99%) compared with SES (55%, p = 0.048). In overlapping stents, endothelialization at the overlapping zone was significantly greater in GS+GS (95 ± 6%) and GS+SES (79 ± 5%) compared with the SES+SES (36 ± 14%) group (p = 0.007). In phase 2, SES–anti-CD34 resulted in increased endothelialization compared with SES alone at 3 days (SES–anti-CD34 36 ± 26%; SES 7 ± 3%; and GS 76 ± 8%; p = 0.01), and 14 days (SES–anti-CD34 82 ± 8%; SES 53 ± 20%; and GS 98 ± 2%; p = 0.009).

Conclusions: Immobilization of anti-CD34 antibody on SES enhances endothelialization and may potentially be an effective therapeutic alternative to improve currently available drug-eluting stents.

Key Words: stent • vascular healing • anti-CD34 antibody • sirolimus • EPC

Abbreviations and Acronyms   BMS = bare-metal stent(s)   CM = confocal microscopy   EC = endothelial cell   EPC = endothelial progenitor cell   GS = Genous stent(s)   HCAEC = human coronary artery endothelial cell   PECAM = platelet endothelial cell adhesion molecule   SEM = scanning electron microscope   SES = sirolimus-eluting stent(s)   SES–anti-CD34 = sirolimus-eluting stents with immobilized anti-CD34 antibody

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