Local Angiopeptin Delivery Using Coated Stents Reduces Neointimal Proliferation in Overstretched Porcine Coronary...

BACKGROUND: Systemic administration of angiopeptin has been shown to inhibit myointimal thickening after arterial injury in several animal species. METHODS AND RESULTS: To explore to what extent high and long-lasting local concentrations of angiopeptin influence the healing process after vascular injury, tantalum balloon-expandable stents were first coated with a polymer loaded with angiopeptin 250 µg. Implantation of these stents in porcine coronary arteries resulted in tissue concentrations of 10.7 pg/ml wet weight in the stented arterial segment 24 hours after stent implantation, gradually declining to 2.0 pg/ml wet weight at day 8. Finally, 20 pigs were randomly treated with either an angiopeptin-loaded or a blank-coated stent. At baseline, the angiographic parameters were similar between both groups but, after 6 weeks, the minimal luminal diameter of the stented arterial segment was larger in the angiopeptin-treated pigs when compared to controls (2.20 +/- 0.57 mm vs 1.57 +/- 0.68 mm, p < 0.01) This angiographic finding was confirmed by post-mortem morphometry where the respective lumen area values were 1.00 +/- 0.54 mm2 and 0.43 +/- 0.28 mm2 (p < 0.01). CONCLUSION: Polymer coated stents can be loaded with angiopeptin, which after implantation in porcine right coronary arteries result in high local tissue concentrations gradually declining over more than 8 days. These high local concentrations inhibit myointimal proliferation induced by poly(organo)phosphazene coated overstretched stents.