Single-dose intramuscular administration of sustained-release Angiopeptin reduces neointimal hyperplasia in a porcine coronary in-stent restenosis model

Mun K. Hong, Kenneth M. Kent, Fermin O. Tio, Marie Foegh, Ran Kornowski, Orville Bramwell, Seedabarum S. Cathapermal, Martin B. Leon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background. In-stent restenosis results primarily from neointimal hyperplasia. In a previous study we showed that continuous subcutaneous Angiopeptin infusion for 1 week significantly reduces neointimal hyperplasia in a porcine coronary overstretch in-stent restenosis model. The present study evaluated the relative efficacy of immediate-release and sustained-release Angiopeptin in the same model. Methods. Thirty pigs (n = 10 in each group) were randomly assigned to three groups: controls receiving no Angiopeptin (Group 1); a sustained-release treatment group receiving one time intramuscular administration of 20 mg of Angiopeptin (Group 2); and a systemic treatment group receiving continuous Angiopeptin over a 1-week period via a subcutaneous osmotic pump (200 μg/kg total dose) (Group 3). One oversized Palmaz-Schatz stent (mean stent/artery = 1.25) was subsequently implanted in the left anterior descending coronary artery. The degree of neointimal reaction was evaluated 4 weeks later by angiography (maximal per cent diameter stenosis) and histology (maximal neointimal area corrected for injury score). Results. A trend towards a reduction in diameter stenosis was observed by angiography, despite a similar degree of injury (25 ± 17% in Group 1, 13 ± 8% in Group 2, and 14 ± 9% in Group 3; P = 0.072 by ANOVA). Histology demonstrated that both Angiopeptin treatment strategies significantly reduced in-stent neointimal area compared with the control group (1.65 ± 0.97 mm2 in Group 1 versus 0.93 ± 0.41 mm2 in Group 2 versus 0.85 ± 0.28 mm2 in Group 3; P = 0.016 by ANOVA). Measurement of plasma Angiopeptin levels revealed comparable levels in both treatment groups, which persisted for up to 2 weeks. Conclusions. This study shows that single-dose intramuscular administration of sustained-release Angiopeptin reduces in-stent restenosis as effectively as the prolonged systemic treatment requiring a subcutaneous pump. Thus, a practical, effective, pharmacologic therapy for preventing in-stent restenosis may be available and should be evaluated in patients.

Original languageEnglish
Pages (from-to)101-104
Number of pages4
JournalCoronary Artery Disease
Volume8
Issue number2
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • Angiopeptin
  • Neointimal hyperplasia
  • Porcine coronary artery
  • Restenosis
  • Stent

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