title: Imatinib mesylate-incorporated nanoparticle-eluting stent attenuates in-stent neointimal formation in porcine coronary arteries.
abstract: OBJECTIVE
  The use of currently marketed drug-eluting stents (DES) presents safety concerns, including an increased risk for late thrombosis in the range of 0.6% per year in patients, including acute coronary syndrome, which is thought to result from delayed endothelial healing effects. A new DES system targeting vascular smooth muscle cells without adverse effects on endothelial cells is therefore needed. Platelet-derived growth factor (PDGF) plays a central role in the pathogenesis of restenosis; therefore, we hypothesized that imatinib mesylate (PDGF receptor tyrosine kinase inhibitor) encapsulated bioabsorbable polymeric nanoparticle (NP)-eluting stent attenuates in-stent neointima formation.
  
  
  METHODS
  Effects of imatinib-incorporated NP-eluting stent on neointima formation and endothelial healing were examined in a pig coronary artery stent model. Effects of imatinib-NP were also examined in cultured cells.
  
  
  RESULTS
  In a cultured cell study, imatinib-NP attenuated the proliferation of vascular smooth muscle cells associated with inhibition of the target molecule (phosphorylation of PDGF receptor-β), but showed no effect on endothelial proliferation. In a pig coronary artery stent model, imatinib-NP-eluting stent markedly attenuated in-stent neointima formation and stenosis by approximately 50% as assessed by angiographic, histopathological, and intravascular ultrasound imaging analyses. Imatinib-NP-eluting stent also attenuated MAP kinase activity, but did not affect inflammation and re-endothelialization.
  
  
  CONCLUSIONS
  These data suggest that suppression of neointima formation by a imatinib-NP-eluting stent holds promise as a molecular-targeting NP delivery system for preventing in-stent restenosis.
authors: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Seigo
authors: S
authors: Masuda
authors: Kaku
authors: K
authors: Nakano
authors: Kouta
authors: K
authors: Funakoshi
authors: Gang
authors: G
authors: Zhao
authors: Wei
authors: W
authors: Meng
authors: Satoshi
authors: S
authors: Kimura
authors: Tetsuya
authors: T
authors: Matoba
authors: Miho
authors: M
authors: Miyagawa
authors: Eiko
authors: E
authors: Iwata
authors: Kenji
authors: K
authors: Sunagawa
authors: Kensuke
authors: K
authors: Egashira
mesh_terms: D000818:Animals; D001158:Arteries / Q000166:cytology* / Q000378:metabolism; D001549:Benzamides; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology* / Q000378:metabolism; D054855:Drug-Eluting Stents; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D053758:Nanoparticles; D010879:Piperazines / Q000008:administration & dosage* / Q000737:chemistry; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage* / Q000737:chemistry; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D013552:Swine; D017539:Tunica Intima
chemical_list: D001549:Benzamides; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D020797:Receptor, Platelet-Derived Growth Factor beta