Development of Nanotechnology Based Less Invasive Therapy for Vein Graft Failure

• Project/Area Number: 20790992
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Thoracic surgery
• Research Institution: Kyushu University
• Principal Investigator: KIMURA Satoshi Kyushu University, 大学院・医学研究院, 共同研究員 (50467916)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 心臓大血管外科学 / ナノテクノロジー / 静脈グラフト

Research 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.

Research Products

• [Journal Article] Formulation of nanoparticle-eluting stents by a cationic electrodeposition coating technology: efficient nano-drug delivery via bioabsorbable polymeric nanoparticle-eluting stents in porcine coronary arteries. (2009)
  • Author(s): Nakano K, Egashira K, Masuda S, Funakoshi K, Zhao G, Kimura S, Matoba T, Sueishi K, Endo Y, Kawashima Y, Hara K, Tsujimoto H, Tominaga R, Sunagawa K
  • Journal Title: JACC Cardiovasc Interv. 2(4) Pages: 277-283
• [Journal Article] Nanoparticle-mediated delivery of nuclear factor kappaB decoy into lungs ameliorates monocrotaline-induced pulmonary arterial hypertension. (2009)
  • Author(s): Kimura S, Egashira K, Chen L, Nakano K, Iwata E, Miyagawa M, Tsujimoto H, Hara K, Morishita R, Sueishi K, Tominaga R, Sunagawa K
  • Journal Title: Hypertension 53(5) Pages: 877-883
• [Journal Article] Local Delivery of Imatinib Mesylate (STI571) Incorporated Nanoparticle Ex Vivo Suppresses Vein Graft Neointima Formation. (2009)
  • Author(s): Kimura S, et al.
  • Journal Title: Circulation. 118
  • Peer Reviewed
• [Journal Article] Nanoparticle-Mediated Delivery of Nuclear Factor κB Decoy Into Lungs Ameliorates Monocrotaline-Induced Pulmonary Arterial. (2009)
  • Author(s): Kimura S, et al.
  • Journal Title: Hypertension. 53(5) Pages: 877-883
  • Peer Reviewed
• [Journal Article] Formulation of nanoparticle-eluting stents by a cationic electrodeposit coating technology : Efficient and safe nano-drug delivery via bioabsorbable polymeric nanoparticle-eluting stents in porcine coronary arteries. (2009)
  • Author(s): Nakano K, et al.
  • Journal Title: JACC : Cardiovascular Intervention 2(4) Pages: 277-283
  • Peer Reviewed
• [Journal Article] Nanoparticle-Mediated Delivery of Nuclear Factor κB Decoy Into Lungs Ameliorates Monocrotaline-Induced Pulmonary Arterial (2009)
  • Author(s): Kimura S, et.al.
  • Journal Title: Hypertension (in press)
  • Peer Reviewed
• [Journal Article] Formulation of nanoparticle-eluting stents by a cationic electrodeposit coating technology : Efficient and safe nano-drug delivery via bioabsorbable polymeric nanoparticle-eluting stents in porcine coronary arteries (2009)
  • Author(s): Nakano K, et.al.
  • Journal Title: J Am Coll Cardiol (in press)
  • Peer Reviewed
• [Journal Article] Local delivery of imatinib mesylate (STI571)-incorporated nanoparticle ex vivo suppresses vein graft neointima formation. (2008)
  • Author(s): Kimura S, Egashira K, Nakano K, Iwata E, Miyagawa M, Tsujimoto H, Hara K, Kawashima Y, Tominaga R, Sunagawa K
  • Journal Title: Circulation 118(14Suppl)
• [Journal Article] Local Delivery of Imatinib Mesylate (STI571) Incorporated Nanoparticle Ex Vivo Suppresses Vein Graft Neointima Formation (2008)
  • Author(s): Kimura S, et.al.
  • Journal Title: Circulation 118
  • Peer Reviewed
• [Presentation] Single Intratracheal Instillation of Bioabsorbable Nanoparticle Incorporated with Statin Ameliorates Monocrotaline-induced Pulmonary Arterial Hypertension and Improved Survival - An Innovative Therapeutic Approach for Pulmonary Arterial Hypertension - (2009)
  • Author(s): Chen L, Egashira K, Kimura S, Nakano K, Iwata E, Miyagawa M, Sunagawa K
  • Organizer: World Hypertension Congress
  • Place of Presentation: Beijing, China
  • Year and Date: 2009-10-29
• [Presentation] Single Intratracheal Instillation of Bioabsorbable Nanoparticle Incorporated with Statin Ameliorates Monocrotaline-induced Pulmonary Arterial Hypertension and Improved Survival-An Innovative Therapeutic Approach for Pulmonary Arterial Hypertension- (2009)
  • Author(s): Chen L, et al.
  • Organizer: World Hypertension Congress
  • Place of Presentation: Beijing, China
  • Year and Date: 2009-10-29
• [Presentation] Single Intratracheal Instillation of Bioabsorbable Nanoparticle Incorporated with Statin Ameliorates Monocrotaline-induced Pulmonary Arterial Hypertension and Improved Survival - An Innovative Therapeutic Approach for Pulmonary Arterial Hypertension - (2008)
  • Author(s): Chen L, Egashira K, Kimura S, Nakano K, Iwata E, Miyagawa M, Sunagawa K
  • Organizer: 第12回Molecular Cardiovascular Conference
  • Place of Presentation: 北海道
  • Year and Date: 2008-09-06
• [Presentation] Single Intratracheal Instillation of Bioabsorbable Nanoparticle Incorporated with Statin Ameliorates Monocrotaline-induced Pulmonary Arterial Hypertension and Improved Survival-An Innovative Therapeutic Approach for Pulmonary Arterial Hypertension (2008)
  • Author(s): Chen L, et.al.
  • Organizer: 第12回Molecular Cardiovascular Conference
  • Place of Presentation: 北海道
  • Year and Date: 2008-09-06
• [Remarks]
  • URL: http://www.med.kyushu-u.ac.jp/cardiol/
• [Remarks]
  • URL: http://www.med.kyushu-u.ac.jp/cardiol/