A novel drug-eluting stent coated with an integrin-binding cyclic Arg-Gly-Asp peptide inhibits neointimal hyperplasia by recruiting endothelial progenitor cells.
OBJECTIVE
Novel stents loaded with an integrin-binding cyclic Arg-Gly-Asp peptide (cRGD) were analyzed for their potential to limit coronary neointima formation and to accelerate endothelialization by attracting endothelial progenitor cells (EPCs).


BACKGROUND
Re-endothelialization is important for healing after arterial injury.


METHODS
Effects of cRGD on EPC number, recruitment in flow, and invasion were analyzed in vitro. A durable polymer coating containing 67 microg cRGD per stent was developed for Guidant Tetra stents. Twelve cRGD-loaded polymer, 12 unloaded polymer, and 12 bare metal stents were deployed in porcine coronary arteries. Quantification of cRGD in peri-stent tissue was established by high-performance liquid chromatography (HPLC) and mass spectrometry (MS). Histomorphometry and immunostaining were performed after 4 and 12 weeks. Recruitment of labeled porcine EPCs was assessed 7 days after intracoronary infusion.


RESULTS
The cRGD clearly supported the outgrowth, recruitment, and migration of EPCs in vitro. At 4 weeks, there was no difference for mean neointimal area and percent area stenosis in the cRGD-loaded, polymer, or bare metal stent group. At 12 weeks, neointimal area (2.2 +/- 0.3 mm2) and percent area stenosis (33 +/- 5%) were significantly reduced compared with polymer stents (3.8 +/- 0.4 mm2, 54 +/- 6%; p = 0.010) or bare metal stents (3.8 +/- 0.3 mm2, 53 +/- 3%; p < 0.001). The HPLC/MS confirmed cRGD tissue levels of 1 to 3 mug/stent at 4 weeks, whereas cRGD was not detectable at 12 weeks. Staining for CD34 and scanning electron microscopy indicated enhanced endothelial coverage on cRGD-loaded stents at 4 weeks associated with a significant increase in the early recruitment of infused EPCs.


CONCLUSIONS
Stent coating with cRGD may be useful for reducing in-stent restenosis by accelerating endothelialization.
Blindt
Rüdiger
R
Department of Cardiology, University Hospital Aachen, Aachen, Germany. ruediger.blindt@post.rwth-aachen.de
Vogt
Felix
F
Astafieva
Irina
I
Fach
Christian
C
Hristov
Mihail
M
Krott
Nicole
N
Seitz
Berthold
B
Kapurniotu
Aphrodite
A
Kwok
Connie
C
Dewor
Manfred
M
Bosserhoff
Anja-Katrin
AK
Bernhagen
Jürgen
J
Hanrath
Peter
P
Hoffmann
Rainer
R
Weber
Christian
C