Local delivery of imatinib mesylate (STI571)-incorporated nanoparticle ex vivo suppresses vein graft neointima formation.

Satoshi Kimura, Kensuke Egashira, Kaku Nakano, Eiko Iwata, Miho Miyagawa, Hiroyuki Tsujimoto, Kaori Hara, Yoshiaki Kawashima, Ryuji Tominaga, Kenji Sunagawa

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Abstract

BACKGROUND: Clinical outcome of surgical revascularization using autologous vein graft is limited by vein graft failure attributable to neointima formation. Platelet-derived growth factor (PDGF) plays a central role in the pathogenesis of vein graft failure. Therefore, we hypothesized that nanoparticle (NP)-mediated drug delivery system of PDGF-receptor (PDGF-R) tyrosine kinase inhibitor (imatinib mesylate: STI571) could be an innovative therapeutic strategy. METHODS AND RESULTS: Uptake of STI571-NP normalized PDGF-induced cell proliferation and migration. Excised rabbit jugular vein was treated ex vivo with PBS, STI571 only, FITC-NP, or STI571-NP, then interposed back into the carotid artery position. NP was detected in many cells in the neointima and media at 7 and 28 days after grafting. Significant neointima was formed 28 days after grafting in the PBS group; this neointima formation was suppressed in the STI571-NP group. STI571-NP treatment inhibited cell proliferation and phosphorylation of the PDGF-R-beta but did not affect inflammation and endothelial regeneration. CONCLUSIONS: STI571-NP-induced suppression of vein graft neointima formation holds promise as a strategy for preventing vein graft failure.

Original languageEnglish
Pages (from-to)S65-70
JournalCirculation
Volume118
Issue number14 Suppl
DOIs
Publication statusPublished - Sep 30 2008

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All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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