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  • Title: A novel drug-eluting stent coated with an integrin-binding cyclic Arg-Gly-Asp peptide inhibits neointimal hyperplasia by recruiting endothelial progenitor cells.
    Author: Blindt R, Vogt F, Astafieva I, Fach C, Hristov M, Krott N, Seitz B, Kapurniotu A, Kwok C, Dewor M, Bosserhoff AK, Bernhagen J, Hanrath P, Hoffmann R, Weber C.
    Journal: J Am Coll Cardiol; 2006 May 02; 47(9):1786-95. PubMed ID: 16682302.
    Abstract:
    OBJECTIVES: 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.
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