title: Efficient inhibition of in-stent restenosis by controlled stent-based inhibition of elastase: a pilot study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Biodegradable microspheres containing the potent elastase inhibitor alpha-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).
  
  
  CONCLUSIONS
  Stent-based controlled release of elastase inhibitor may significantly reduce ECM degradation and might limit in-stent restenosis.
authors.affiliation: Department of Cardiovascular and Interventional Radiology, Program in Human Gene Therapy, Stanford University School of Medicine, 300 Pasteur Drive, H3648, Stanford, California 94305, USA.
authors.forename: Fumikiyo
authors.initials: F
authors.lastname: Ganaha
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohashi
authors.forename: Young So
authors.initials: YS
authors.lastname: Do
authors.forename: Jane
authors.initials: J
authors.lastname: Lee
authors.forename: Koji
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Minamiguchi
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Elkins
authors.forename: Diba
authors.initials: D
authors.lastname: Sameni
authors.forename: Shoreh
authors.initials: S
authors.lastname: Modanlou
authors.forename: Mir
authors.initials: M
authors.lastname: Ali
authors.forename: Edward Y
authors.initials: EY
authors.lastname: Kao
authors.forename: Mark A
authors.initials: MA
authors.lastname: Kay
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Waugh
authors.forename: Michael D
authors.initials: MD
authors.lastname: Dake
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004549:Elastin / Q000187:drug effects; D005263:Femoral Artery / Q000601:surgery; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D066298:In Vitro Techniques; D008297:Male; D008488:Medical Illustration; D008863:Microspheres; D023421:Models, Animal; D010196:Pancreatic Elastase / Q000187:drug effects*; D010865:Pilot Projects; D011817:Rabbits; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D015607:Stents; D013997:Time Factors; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D004549:Elastin; D010196:Pancreatic Elastase