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(Circulation. 2008;118:S65-S70.)
© 2008 American Heart Association, Inc.

Myocardial Protection, Perioperative Management, and Vascular Biology

Local Delivery of Imatinib Mesylate (STI571)-Incorporated Nanoparticle Ex Vivo Suppresses Vein Graft Neointima Formation

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

From the Department of Cardiovascular Medicine (K.E., K.N., E.I., M.M., K.S.) and Surgery (S.K., R.T.), Graduate School of Medical Science, Kyushu University, Fukuoka, Japan; Hosokawa Powder Technology Research Institute (H.T., K.H.), Osaka, Japan; and the School of Pharmaceutical Science (Y.K.), Aichi Gakuin University, Aichi, Japan.

Correspondence to Kensuke Egashira, MD, PhD, Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail egashira{at}cardiol.med.kyushu-u.ac.jp

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-β 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.

Key Words: nanotechnology • drug delivery system • grafting • platelet-derived factors • signal transduction