Efficient inhibition of in-stent restenosis by controlled stent-based inhibition of elastase: A pilot study

Fumikiyo Ganaha, Kazuo Ohashi, Young So Do, Jane Lee, Koji Sugimoto, Hiroki Minamiguchi, Christopher J. Elkins, Diba Sameni, Shoreh Modanlou, Mir Ali, Edward Y. Kao, Mark A. Kay, Jacob M. Waugh, Michael D. Dake

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

PURPOSE: It is proposed that local elastase inhibition could suppress the extracellular matrix (ECM) degradation and subsequent smooth muscle cell migration and limit subsequent in-stent restenosis. This study evaluated the effect of stent-based controlled elastase inhibition on restenosis after stent implantation in a rabbit model. MATERIALS AND METHODS: Biodegradable microspheres containing the potent elastase inhibitor α-1-antitrypsin (AAT) were prepared. Daily release of AAT from the microspheres was confirmed in vitro. The microspheres were loaded into stents with an abluminal polymer reservoir. Implantation of the stent with AAT microspheres and blank microspheres (control) was performed in the abdominal aortae of six rabbits in each group. After stent deployment, all stents were overdilated to 125% diameter. Stent-implanted arteries were harvested after 7 days (n = 3 each) or 28 days (n = 3 each). To assess the effect of local delivery of AAT, elastase activity and elastin content of the stent-implanted aortae were analyzed. As an endpoint, intima-to-media (I/M) ratio was determined in the 7-day and 28-day specimens. RESULTS: Significant inhibition of elastase was confirmed in treated vessels versus controls at 7 days after stent implantation (P < .05). This reduction in elastase activity was sufficient to afford early and late reduction of in-stent neointima. Plaque progression in the 28-day specimens decreased to 67% with elastase inhibition relative to controls (P < .05). CONCLUSION: Stent-based controlled release of elastase inhibitor may significantly reduce ECM degradation and might limit in-stent restenosis.

Original languageEnglish (US)
Pages (from-to)1287-1293
Number of pages7
JournalJournal of Vascular and Interventional Radiology
Volume15
Issue number11
DOIs
StatePublished - Nov 2004
Externally publishedYes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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    Ganaha, F., Ohashi, K., Do, Y. S., Lee, J., Sugimoto, K., Minamiguchi, H., Elkins, C. J., Sameni, D., Modanlou, S., Ali, M., Kao, E. Y., Kay, M. A., Waugh, J. M., & Dake, M. D. (2004). Efficient inhibition of in-stent restenosis by controlled stent-based inhibition of elastase: A pilot study. Journal of Vascular and Interventional Radiology, 15(11), 1287-1293. https://doi.org/10.1097/01.RVI.0000141340.67588.4F