New Gene Therapy-Controlled Release of siRNA as to Midkine Inhibits the Intimal Hyperplasia in Vein Grafts

• Project/Area Number: 18390344
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Nagoya University
• Principal Investigator: KOMORI Kimihiro Nagoya University, 大学院・医学系研究科, 教授 (40225587)
• Co-Investigator(Kenkyū-buntansha): KADOMATSU Kenji 名古屋大学, 大学院・医学系研究科, 教授 (80204519) ; MUROHARA Toyoaki 名古屋大学, 大学院・医学系研究科, 教授 (90299503) ; YAMAMOTO Kiyohito 名古屋大学, 医学部・附属病院, 講師 (10298359) ; KOBAYASHI Masayoshi 名古屋大学, 医学部・附属病院, 助教 (60329381)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,620,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥2,220,000); Fiscal Year 2008: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2007: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2006: ¥8,000,000 (Direct Cost: ¥8,000,000)
• Keywords: ステント / 血管内膜肥厚 / Midkine / 遺伝子治療 / 再狭窄 / ステント再狭窄

Research Abstract

Midkine(MK)はヘパリン結合性増殖因子であり、炎症に関与することがMK欠損マウスでの研究で証明されている。本研究では、高脂血症ウサギモデルを用いて、ステント留置血管におけるMK発現と新生内膜の関係について検討し、MKはステント留置後の新生内膜増殖において浸潤マクロファージを介して重要な役割を担っていることを明らかにした。今後は、MKを標的分子とした薬剤溶出ステントによるステント再狭窄予防への臨床応用が期待される。

Research Products

• [Journal Article] Midkine is expressed by infiltrating macrophages in in-stent restenosis In hypercholesterolemic rabbits (2008)
  • Author(s): Narita H,Sen C,Komori K, Kadomatsu K
  • Journal Title: J Vasc Surg 47 Pages: 1322-9
  • Peer Reviewed
• [Journal Article] Surgical Management of Abdominal Aortic Aneurysm Associated with Polycystic Kidney Disease : Report of Two Cases (2008)
  • Author(s): Inoguch H, Komori K, Maehara Y
  • Journal Title: Surgery Today 38 Pages: 253-257
  • NAID: 10021284222
  • Peer Reviewed
• [Journal Article] Pitavastain Inhibits Intimal Hyperplaisa in Rabbit Vein Graft (2008)
  • Author(s): Fujita H, Banno H, Yamanouchi D ,Kobayashi M, Yamamoto K, Komori K
  • Journal Title: J Surg Res 148 Pages: 238-243
  • Peer Reviewed
• [Journal Article] Serum procalcitonin(PCT)is a reliable marker for ischemic omplication of the intestine after open abdominal aortic surgery (2008)
  • Author(s): Nagata J, Kobayashi M, Nishikimi N, Komori K
  • Journal Title: Eur J Vasc Endovasc Surg 35 Pages: 694-697
  • Peer Reviewed
• [Journal Article] Midkine is expressed by infiltrating macrophages in in-stent restenosis In hypercholes terolemic rabbits. (2008)
  • Author(s): Narita H, Sen C, Komori K, Kadomatsu K.
  • Journal Title: J Vase Surg 47 Pages: 1322-1329
  • Peer Reviewed
• [Journal Article] Surgical Management of Abdominal Aortic Aneurysm Associated with Polycystic Kidney Disease : Report of Two Cases. (2008)
  • Author(s): Inoguch H, Komori K, Maehara Y
  • Journal Title: Surgery Today 38 Pages: 253-257
  • NAID: 10021284222
  • Peer Reviewed
• [Journal Article] Pitavastain Inhibits Intimal Hyperplaisa in Rabbit Vein Graft. (2008)
  • Author(s): Fujita H, Banno H, Yamanouchi D, Kobavashi M, Yamamoto K, Komori K
  • Journal Title: J Surg Res 148 Pages: 238-243
  • Peer Reviewed
• [Journal Article] Serum procalcitonin(PCT) is a reliable marker for ischemic complication of the intestine after open abdominal aortic surgery (2008)
  • Author(s): Nagata J, Kobayashi M, Nishikimi N, Komori K
  • Journal Title: Eur J Vase Endovasc Surg 35 Pages: 694-697
  • Peer Reviewed
• [Journal Article] Celiprolol reduces the intimal thickening of autogenous vein grafts via an enhancement of nitric oxide function through an inhibition of superoxide production (2007)
  • Author(s): Hattori K, Yamanouchi D, Banno H, Kobayashi M, Yamamoto K, Kajikuri J, Itoh T, Komori K
  • Journal Title: J Vasc Surg 46 Pages: 116-23
  • Peer Reviewed
• [Journal Article] Rho-Kinase phosphorylates eNOS at threonine 495 in endothelial cells (2007)
  • Author(s): Sugimoto M, Nakayama M, Goto M, AmanoM, Komori K, Kaibuchi K
  • Journal Title: BIOCHEM BIOPH RES CO 361 Pages: 462-467
  • Peer Reviewed
• [Journal Article] Angiotensin II-induced growth of vascular smooth muscle cells is associated with modulation of cell surface area and PDGF receptor expression (2007)
  • Author(s): Kuma S, Oki E, Onohara T, Komori K, Maehara Y
  • Journal Title: Clin Exp Pharamacolo P 34 Pages: 153-160
  • Peer Reviewed
• [Journal Article] Safety and Efficacy of Autologous Progenitor Cell Transplantation for Therapeutic Angiogenesis in Patients with Critical Limb Ishemia (2007)
  • Author(s): Kajiguchi M, Kondo T, Izawa H, Kobayashi M, Yamamoto K, Shintani S, Numaguchi Y, Naoe T, Takamatsu J, Komori K, Murohara T
  • Journal Title: Circulation J 71 Pages: 196-201
  • Peer Reviewed
• [Journal Article] In Vivo Reduction of the Nuclear Factor-kB Activity Using Synthetic cis-Element Decoy Oligonucleotides Suppresses Intimal Hyperplasia in the Injured Carotid Arteries in Rabbits (2007)
  • Author(s): Takeuchi K, Itoh H, Yonemitsu Y, Matsumoto T, Kume M, Komori K, Maehara Y
  • Journal Title: Surg Today 37 Pages: 575-583
  • Peer Reviewed
• [Journal Article] Comparison of Doppler and Oscillometric Ankle Blood Pressure Measurement in Patients With Angiographically Documented Lower Extremity Arterial Occlusive Disease (2007)
  • Author(s): Nukumizu Y, Matsushuta M, Sakurai T, Kobayashi M, Nishikimi N, Komori K
  • Journal Title: Angiology 58 Pages: 303-308
  • Peer Reviewed
• [Journal Article] Celiprolol reduces the intimal thickening of autogenous veingrafts via an enhancement of nitric oxide function through aninhibition of superoxide production. (2007)
  • Author(s): Hattori K
  • Journal Title: J Vasc Surg 46 Pages: 116-123
  • Peer Reviewed
• [Journal Article] Rho-Kinase phosphorylates eNOS at threonine 495 in endothelialcell. (2007)
  • Author(s): Sugimoto M
  • Journal Title: BIOCHEM BIOPH RES CO 361 Pages: 462-467
  • Peer Reviewed
• [Journal Article] Comparison of Doppler and Oscillometric Ankle Blood Pressure Measurement in Patients With Angiographically Documented Lower Extremity Arterial Occlusive Disease. (2007)
  • Author(s): Nukumizu Y
  • Journal Title: Angiology 58 Pages: 303-308
  • Peer Reviewed
• [Journal Article] Safety and Efficacy of Autologous Progenitor Cell Transplantation for Therapeutic Angiogenesis in Patients with Critical Limb Ishemia. (2007)
  • Author(s): Kajiguchi M
  • Journal Title: Circulation J 71 Pages: 196-201
• [Journal Article] Clinical Protocol for Angiogenesis by Intramyocardial Injection of Autologous Bone Marrow Mononuclear Cells in Patients With Severe Coronary Artery Disease-TACT-NAGOYA-HEART- (2006)
  • Author(s): Izawa H, Kondo T, Usui A, Yamamoto K, Shintani S, Inden Y, Isobe S, Unno K, Kajiguchi M, Kato T, Noda A, Okumura K, Naoe T, Takamatsu J, Komori K, Ueda Y, Murohara T
  • Journal Title: Circulation J 70(9) Pages: 1180-1183
  • NAID: 110004814895
  • Peer Reviewed
• [Journal Article] The Retroperitoneum Protects Prosthetic Graft Material from Intraperitoneal contamination : An Experimental Study (2006)
  • Author(s): Fujishiro K, Nishikimi N, Watanabe N, Sakurai T, Komori K, Ohta M
  • Journal Title: Eur J Vasc Endovasc Surg 31 Pages: 280-283
  • Peer Reviewed
• [Journal Article] The Retroperitoneum Protects Prosthetic Graft Material from Intraperitoneal contamination : An Experimental Study. (2006)
  • Author(s): Fujishiro K
  • Journal Title: Eur J Vase Endovasc Surg 31 Pages: 280-283
• [Journal Article] Bi-phasic activation of eNOS in response to uniaxial cyclic stretch is mediated by differential mechanisms in BAECs. (2006)
  • Author(s): Takeda H
  • Journal Title: Life Sci 79(3) Pages: 233-239
• [Journal Article] Combination of In Vivo Angiopoientin-1 Gene Transfer and Autologous Bone Marrow Cell Implantation for Functional Therapeutic Angiogenesis. (2006)
  • Author(s): Kobayashi K
  • Journal Title: Arterioscl Throm Vas Biol 26(7) Pages: 1465-1472
• [Journal Article] Long-term inhibition of Rho-kinase suppresses intimal thickening in autologous vein grafts in rabbits. (2006)
  • Author(s): Furuyama T
  • Journal Title: J Vasc Surg 43(6) Pages: 1249-1256
• [Journal Article] Controlled Release of siRNA as to Midkine Attenuates Intimal Hyperplasia in Vein Grafts. (2006)
  • Author(s): Bannno H
  • Journal Title: J Vase Surg 44(3) Pages: 633-641
• [Presentation] 末梢動脈閉鎖症の診断 : 治療の決めかた (2008)
  • Author(s): 古森公浩
  • Organizer: 第25回小倉ライブ
  • Place of Presentation: リーガロイヤルホテル小倉
  • Year and Date: 2008-06-01
• [Presentation] 末梢動脈閉塞症の診断 : 治療の決めかた (2008)
  • Author(s): 古森公浩
  • Organizer: 第25回小倉ライブ
  • Place of Presentation: リーガロイヤルホテル小倉
  • Year and Date: 2008-06-01
• [Presentation] 閉塞性動脈硬化症の手術におけるpit fallと対策 (2008)
  • Author(s): 古森公浩
  • Organizer: 第7回日本血管外科学会
  • Place of Presentation: アルカディア市ケ谷(東京)
  • Year and Date: 2008-04-16
• [Presentation] 閉塞性動脈硬化症の手術におけるpit fallと対策 (2008)
  • Author(s): 古森公浩
  • Organizer: 第7回日本血管外科学会
  • Place of Presentation: アルカディア市ケ谷
  • Year and Date: 2008-04-16
• [Presentation] AAAに対する外科的手術-手技と成績- (2008)
  • Author(s): 古森公浩
  • Organizer: 第1回Japan Endovascular Treatment Conference
  • Place of Presentation: ヒルトン東京
  • Year and Date: 2008-04-12
• [Presentation] 末梢動脈疾患(PAD)に対する治療戦略 (2008)
  • Author(s): 古森公浩
  • Organizer: 第7回日本再生医療学会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2008-03-13
• [Presentation] 末梢動脈疾患(Peripheral Arterial disease : PAD)に対する血行再建術-血管内治療と外科的バイパス術 (2008)
  • Author(s): 古森公浩
  • Organizer: 第13回バスキュラーアクセスインターベンション治療研究会
  • Place of Presentation: 津田ホール(東京)
  • Year and Date: 2008-03-01
• [Presentation] 末梢動脈疾患(Peripheral Arterial Disease : PAD)に対する血行再建術-血管内治療と外科的バイパス術- (2007)
  • Author(s): 古森公浩
  • Organizer: 第48回日本脈管学会
  • Place of Presentation: 松本
  • Year and Date: 2007-10-27
• [Presentation] 末梢動脈疾患(Peripheral Arterial Disease:PDA)に対する血行再建術-血管内治療と外科的バイパス術- (2007)
  • Author(s): 古森 公浩
  • Organizer: 第48回日本脈管学会総会
  • Place of Presentation: 松本
  • Year and Date: 2007-10-25
• [Book] 臨床雑誌「外科」 (2009)
  • Author(s): 児玉章朗、古森公浩
  • Publisher: 南江堂
• [Book] 閉塞性動脈硬化症(PAD)診療の実践-間欠性跛行に対するアプローチ- (2009)
  • Author(s): 杉本昌之、古森公浩
  • Publisher: 南江堂
• [Book] 臨床雑誌「外科」 (2009)
  • Author(s): 児玉章朗, 古森公浩
  • Publisher: 南江堂
• [Book] 別冊日本臨床新領域別症候群シリーズ循環器症候群(第2版)III-その他の循環疾患を含めて (2008)
  • Author(s): 児玉章朗、古森公浩
  • Publisher: 日本臨牀社
• [Book] 手術-手術局所解剖アトラス- (2008)
  • Author(s): 児玉章朗、古森公浩
  • Publisher: 金原出版
• [Book] Angiology Frontier (2008)
  • Author(s): 杉本昌之、古森公浩
  • Publisher: メディカルレビュー社
• [Book] 心臓血管外科テクニックII大血管疾患編 (2008)
  • Author(s): 古森公浩
  • Publisher: メディカ出版
• [Book] 別冊日本臨林 新領域別症候群シリーズ循環器症候群(第2版)III-その他の循環疾患を含めて- (2008)
  • Author(s): 児玉章朗, 古森公浩
  • Publisher: 日本臨休社
• [Book] 手術-手術局所解剖アトラス- (2008)
  • Author(s): 児玉章朗, 古森公浩
  • Publisher: 金原出版
• [Book] Angiology Frontier (2008)
  • Author(s): 杉本昌之, 古森公浩
  • Publisher: メディカルレビュー社
• [Book] 血管外科基本手技アトラス (2007)
  • Author(s): 古森公浩
  • Publisher: 南山堂
• [Book] 心臓血管外科テキスト (2007)
  • Author(s): 上遠野由紀、藤田広峰、古森公浩
  • Publisher: 中外医学社
• [Book] 血管外科基本手技アトラス (2007)
  • Author(s): 古森 公浩
  • Total Pages: 247
  • Publisher: 南山堂
• [Book] 大動脈瘤・大動脈解離診断のコツと落とし穴 (2006)
  • Author(s): 古森公浩
  • Publisher: 中山書店
• [Book] NAVIGATOR血栓症ナビゲーター (2006)
  • Author(s): 古森公浩
  • Publisher: メディカルレビュー社
• [Book] 標準血管外科 (2006)
  • Author(s): 古森公浩
  • Publisher: メディカルトリビューン