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CardioVascular and Interventional Radiology

, Volume 30, Issue 6, pp 1192–1200 | Cite as

Antirestenotic Effects of a Novel Polymer-Coated D-24851 Eluting Stent. Experimental Data in a Rabbit Iliac Artery Model

  • Dimitrios N. Lysitsas
  • Christos S. Katsouras
  • John C. Papakostas
  • Ioannis K. Toumpoulis
  • Charalampos Angelidis
  • Petros Bozidis
  • Christopher G. Thomas
  • Konstantin Seferiadis
  • Nikolaos Psychoyios
  • Stathis Frillingos
  • Nikolaos Pavlidis
  • Euaggelos Marinos
  • Lubna Khaldi
  • Dimitris A. Sideris
  • Lampros K. MichalisEmail author
Laboratory Investigation

Abstract

Experimental and clinical data suggest that stents eluting antiproliferative agents can be used for the prevention of in-stent restenosis. Here we investigate in vitro the antiproliferative and apoptotic effect of D-24851 and evaluate the safety and efficacy of D-24851-eluting polymer-coated stents in a rabbit restenosis model (= 53). Uncoated stents (= 6), poly (dl-lactide-co-glycolide) (PLGA)-coated stents (= 7), and PLGA-coated stents loaded with 0.08 ± 0.0025 μM (31 ± 1 μg; low dose; = 7), 0.55 ± 0.02 μM (216 ± 8 μg; high dose; = 6), and 4.55 ± 0.1 μM (1774 ± 39 μg; extreme dose; = 5) of D-24851 were randomly implanted in New Zealand rabbit right iliac arteries and the animals were sacrificed after 28 days for histomorphometric analysis. For the assessment of endothelial regrowth in 90 days, 12 rabbits were subjected to PLGA-coated (= 3), low-dose (= 3), high-dose (= 3), and extreme-dose (= 3) stent implantation. In vitro studies revealed that D-24851 exerts its growth inhibitory effects via inhibition of proliferation and induction of apoptosis without increasing the expression of heat shock protein-70, a cytoprotective and antiapoptotic protein. Treatment with low-dose D-24851 stents was associated with a significant reduction in neointimal area and percentage stenosis only compared with bare metal stents (38% [= 0.029] and 35% [= 0.003] reduction, respectively). Suboptimal healing, however, was observed in all groups of D-24851-loaded stents in 90 days in comparison with PLGA-coated stents. We conclude that low-dose D-24851-eluting polymer-coated stents significantly inhibit neointimal hyperplasia at 28 days through inhibition of proliferation and enhancement of apoptosis. In view of the suboptimal re-endothelialization, longer-term studies are needed in order to establish whether the inhibition of intimal growth is maintained.

Keywords

Neointima Stent Restenosis D-24851 Apoptosis 

Notes

Acknowledgments

This study was funded by the Michaelideion Cardiac Center and the Medispes SW AG, Greece.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Dimitrios N. Lysitsas
    • 1
  • Christos S. Katsouras
    • 1
  • John C. Papakostas
    • 1
  • Ioannis K. Toumpoulis
    • 1
  • Charalampos Angelidis
    • 1
  • Petros Bozidis
    • 1
  • Christopher G. Thomas
    • 1
  • Konstantin Seferiadis
    • 1
    • 2
  • Nikolaos Psychoyios
    • 2
  • Stathis Frillingos
    • 3
  • Nikolaos Pavlidis
    • 4
  • Euaggelos Marinos
    • 5
  • Lubna Khaldi
    • 6
  • Dimitris A. Sideris
    • 1
  • Lampros K. Michalis
    • 1
    • 7
    Email author
  1. 1.Michailideion Cardiac CenterIoanninaGreece
  2. 2.Laboratory of Clinical ChemistryUniversity of Ioannina Medical SchoolIoanninaGreece
  3. 3.Laboratory of Biological ChemistryUniversity of Ioannina Medical SchoolIoanninaGreece
  4. 4.Department of OncologyUniversity of Ioannina Medical SchoolIoanninaGreece
  5. 5.Department of Histology-Embryology, School of MedicineUniversity of AthensAthensGreece
  6. 6.Department of PathologyUniversity Hospital of LarisaLarisaGreece
  7. 7.School of MedicineUniversity Hospital of IoanninaIoanninaGreece

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