Imatinib mesylate-incorporated nanoparticle-eluting stent attenuates in-stent neointimal formation in porcine coronary arteries

Seigo Masuda, Kaku Nakano, Kouta Funakoshi, Gang Zhao, Wei Meng, Satoshi Kimura, Tetsuya Matoba, Miho Miyagawa, Eiko Iwata, Kenji Sunagawa, Kensuke Egashira

研究成果: ジャーナルへの寄稿記事

32 引用 (Scopus)

抄録

Aim: 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-NPeluting 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. Conclusion: 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.

元の言語英語
ページ(範囲)1043-1053
ページ数11
ジャーナルJournal of Atherosclerosis and Thrombosis
18
発行部数12
DOI
出版物ステータス出版済み - 12 22 2011

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Stents
Nanoparticles
Coronary Vessels
Swine
Neointima
Cells
Drug-Eluting Stents
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cultured Cells
Muscle
Imatinib Mesylate
Platelet-Derived Growth Factor Receptors
Platelet-Derived Growth Factor
Acute Coronary Syndrome
Phosphorylation
Endothelial cells
Ultrasonography
Pathologic Constriction
Thrombosis

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine
  • Biochemistry, medical

これを引用

Imatinib mesylate-incorporated nanoparticle-eluting stent attenuates in-stent neointimal formation in porcine coronary arteries. / Masuda, Seigo; Nakano, Kaku; Funakoshi, Kouta; Zhao, Gang; Meng, Wei; Kimura, Satoshi; Matoba, Tetsuya; Miyagawa, Miho; Iwata, Eiko; Sunagawa, Kenji; Egashira, Kensuke.

:: Journal of Atherosclerosis and Thrombosis, 巻 18, 番号 12, 22.12.2011, p. 1043-1053.

研究成果: ジャーナルへの寄稿記事

Masuda, Seigo ; Nakano, Kaku ; Funakoshi, Kouta ; Zhao, Gang ; Meng, Wei ; Kimura, Satoshi ; Matoba, Tetsuya ; Miyagawa, Miho ; Iwata, Eiko ; Sunagawa, Kenji ; Egashira, Kensuke. / Imatinib mesylate-incorporated nanoparticle-eluting stent attenuates in-stent neointimal formation in porcine coronary arteries. :: Journal of Atherosclerosis and Thrombosis. 2011 ; 巻 18, 番号 12. pp. 1043-1053.
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abstract = "Aim: 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-NPeluting 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. Conclusion: 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.",
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T1 - Imatinib mesylate-incorporated nanoparticle-eluting stent attenuates in-stent neointimal formation in porcine coronary arteries

AU - Masuda, Seigo

AU - Nakano, Kaku

AU - Funakoshi, Kouta

AU - Zhao, Gang

AU - Meng, Wei

AU - Kimura, Satoshi

AU - Matoba, Tetsuya

AU - Miyagawa, Miho

AU - Iwata, Eiko

AU - Sunagawa, Kenji

AU - Egashira, Kensuke

PY - 2011/12/22

Y1 - 2011/12/22

N2 - Aim: 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-NPeluting 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. Conclusion: 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.

AB - Aim: 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-NPeluting 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. Conclusion: 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.

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