Stent coated with antibody against vascular endothelial-cadherin captures endothelial progenitor cells, accelerates re-endothelialization, and reduces neointimal formation.
OBJECTIVE
In contrast to CD34, vascular endothelial-cadherin (VE-cadherin) is exclusively expressed on the late endothelial progenitor cells (EPC) whereas not on the early or myeloid EPC. Thus, VE-cadherin could be an ideal target surface molecule to capture circulating late EPC. In the present study, we evaluated whether anti-VE-cadherin antibody-coated stents (VE-cad stents) might accelerate endothelial recovery and reduce neointimal formation through the ability of capturing EPC.


RESULTS
The stainless steel stents were coated with rabbit polyclonal anti-human VE-cadherin antibodies and exposed to EPC for 30 minutes in vitro. The number of EPC that adhered to the surface of VE-cad stents was significantly higher than bare metal stents (BMS) in vitro, which was obliterated by pretreatment of VE-cad stent with soluble VE-cadherin proteins. We deployed VE-cad stents and BMS in the rabbit right and left iliac arteries, respectively. At 48 hours after stent deployment in vivo, CD-31-positive endothelial cells adhered to VE-cad stent significantly more than to BMS. At 3 days, scanning electron microscopy showed that over 90% surface of VE-cad stents was covered with endothelial cells, which was significantly different from BMS. At 42 days, neointimal area that was filled with smooth muscle cells positive for actin or calponin was significantly smaller in VE-cad stents than in BMS by histological analysis (0.95±0.22 versus 1.34±0.43 mm(2), respectively, P=0.02). Immuno-histochemical analysis revealed that infiltration of inflammatory cells was not significantly different between 2 stents.


CONCLUSIONS
VE-cad stents captured EPC successfully in vitro, accelerated endothelial recovery on stent, and eventually reduced neointimal formation in vivo.
National Research Laboratory for Stem Cell Niche, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, Korea 110-744, Korea.
Woo-Hyun
WH
Lim
Won-Woo
WW
Seo
Wonseok
W
Choe
Chan-Koo
CK
Kang
Jonghanne
J
Park
Hyun-Ju
HJ
Cho
San
S
Kyeong
Jin
J
Hur
Han-Mo
HM
Yang
Hyun-Jai
HJ
Cho
Yoon-Sik
YS
Lee
Hyo-Soo
HS
Kim
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D050197:Atherosclerosis / Q000517:prevention & control; D015820:Cadherins / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008670:Metals; D058426:Neointima / Q000473:pathology / Q000517:prevention & control*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011817:Rabbits; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015607:Stents; D000099152:Cadherin 5
D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D018952:Antigens, CD34; D015820:Cadherins; D008670:Metals; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000099152:Cadherin 5