Potent Inhibiting Effect of Activated vitamine D3 on Aortic Aneurysm Dilatation

2019 Fiscal Year Annual Research Report

• Project/Area Number: 17K10753
• Research Institution: Nagoya University
• Principal Investigator: 新美 清章 名古屋大学, 医学部附属病院, 助教 (50467312)
• Co-Investigator(Kenkyū-buntansha): 古森 公浩 名古屋大学, 医学系研究科, 教授 (40225587) ; 坂野 比呂志 名古屋大学, 医学部附属病院, 講師 (80584721) ; 杉本 昌之 名古屋大学, 医学部附属病院, 病院講師 (00447814)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 腹部大動脈瘤 / 活性型ビタミンD / ビタミンD / 動脈硬化 / 炎症メディエーター / M2マクロファージ

Outline of Annual Research Achievements

大動脈瘤関連因子とビタミンDとの関係を明らかにするため、in vitroでJ774A.1マウスマクロファージを使用し、calcitriol投与での炎症メディエーターであるMCP-1、MMP-9,IL-1βの遺伝子発現量を評価したが、MCP-1の遺伝子発現は抑制されたが、IL-1βとMMP-9では促進する結果となり、calcitriolのマクロファージに対する抗炎症効果は確認できなかった。
この課程で、閉塞性呼吸器疾患で用いられるロイコトリエン拮抗薬であるモンテルカスト(Mont)の心血管疾患に対する有効性が報告されていることがわかり、calcitoriolのnegative dataをうけ、抗モンテルカストのマクロファージに対する作用と大動脈瘤に対する治療効果を検討。TNF-αで刺激したマウス由来マクロファージ(M1マクロファージ)をMontと供に培養し,炎症性サイトカインの遺伝子発現を解析.Mont添加マクロファージ(M0マクロファージ)のArginase-1の遺伝子発現及び細胞表面抗原を分析、マウス動脈瘤モデル作製し、28日後に大動脈瘤径,瘤壁の中膜のエラスチンの割合、MMP活性,炎症性サイトカイン、M2マクロファージを測定。
MontはM1マクロファージのMMP2,MMP9,IL-1β,NF-κBの遺伝子発現を有意に抑制し、M0マクロファージのArginase-1の遺伝子発現を有意に促進、Mont群で有意に瘤径拡大が抑制(生食群2.44mm vs Mont群1.59mm,p<0.01)、エラスチン分解が有意に抑えられ(生食群45% vs Mont群56%,p<0.05)、MMP2活性も有意に低下(生食群1234&micro;M vs Mont群734&micro;M,p<0.05)。Mont群で有意にM2マクロファージが増加(生食群7.5% vs Mont群14.7%,p<0.05)。

Research Products

• [Journal Article] Montelukast, a Cysteinyl Leukotriene Receptor 1 Antagonist, Induces M2 Macrophage Polarization and Inhibits Murine Aortic Aneurysm Formation. (2019)
  • Author(s): Kawai Y, Narita Y, Yamawaki-Ogata A, Usui A, Komori K
  • Journal Title: Biomed Res Int. Volume: 2019 Pages: 1-11
  • DOI: 10.1155/2019/9104680
  • Peer Reviewed
• [Journal Article] Proximal Bare Stent May Reduce Bird-Beak Configuration, Which is Associated with Distal Migration of Stent Graft in the Aortic Arch. (2019)
  • Author(s): Banno H, Akita N, Fujii T, Tsuruoka T, Takahashi N, Sugimoto M, Niimi K, Komori K
  • Journal Title: Ann Vasc Surg. Volume: 56 Pages: 108-113
  • DOI: 10.1016/j.avsg.2018.08.081
  • Peer Reviewed
• [Journal Article] Zilver PTX Post-market Surveillance Study of Paclitaxel-Eluting Stents for Treating Femoropopliteal Artery Disease in Japan: 2-Year Results. (2019)
  • Author(s): Kichikawa K, Ichihashi S, Yokoi H, Ohki T, Nakamura M, Komori K, Nanto S, O'Leary EE, Lottes AE, Snyder SA, Dake MD
  • Journal Title: Cardiovasc Intervent Radiol. Volume: 42(3) Pages: 358-364
  • DOI: 10.1007/s00270-018-2110-1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Associations of nutritional status and muscle size with mortality following open aortic aneurysm repair (2019)
  • Author(s): Kodama A, Takahashi N, Sugimoto M, Niimi K, Banno H, Komori K
  • Journal Title: J Vasc Surg. Volume: 70(5) Pages: 1585-1593
  • DOI: 10.1016/j.jvs.2019.01.049
  • Peer Reviewed
• [Presentation] New trial program for educating young vascular surgeons in Japan (2019)
  • Author(s): Komori K
  • Organizer: 13th China Southern Endovascular Congress
  • Int'l Joint Research
• [Presentation] Long-Term Renal Function following Endovascular and open Abdominal Aneurysm Repair (2019)
  • Author(s): Komori K
  • Organizer: 13th China Southern Endovascular Congress
  • Int'l Joint Research
• [Presentation] Diffremce between early and late apontaneouse SAC shrinkage after EVAR (2019)
  • Author(s): Sugimoto M, Takahashi N, Niimi K, Kodama A, Banno H, Komori K
  • Organizer: 33rd Annual Meeting of the European Society for Vascular Surgery
  • Int'l Joint Research
• [Presentation] Impact of the left renal vein division on tatal and split renal function after open of PARA- and Juxtarenal aortic aneurysm (2019)
  • Author(s): Sugimoto M, Takahashi N, Niimi K, Kodama A, Banno H, Komori K
  • Organizer: 33rd Annual Meeting of the European Society for Vascular Surgery
  • Int'l Joint Research
• [Presentation] outcomes of celiac artery coverage during thoracic endovascular aortic repair (2019)
  • Author(s): Banno H, Ikeda S, Kawai Y, Meshii K, Takahashi N, Sugimoto M, Niimi K, Kodama A, Komori K
  • Organizer: 33rd Annual Meeting of the European Society for Vascular Surgery
  • Int'l Joint Research
• [Presentation] The efficacy of endovascular laser ablation alone as a treatment for varicose veins (2019)
  • Author(s): Kawai,Y Aikawa K, Komori K
  • Organizer: 33rd Annual Meeting of the European Society for Vascular Surgery
  • Int'l Joint Research
• [Presentation] Long-Term (5 Years) Effectiveness Of Zilver PTX Drug Eluting Stents (DESs) For Fempop In Stent Restenosis (ISR): From The Japanese Post Market Surveillance Study (2019)
  • Author(s): Komori K
  • Organizer: VEITH symposium Connecting The Vascular Community 46th Annual
  • Int'l Joint Research
• [Presentation] Depleted Nutritional Status And Muscle Mass Increases The Risk Of Open AAA Repair:What About With EVAR (2019)
  • Author(s): Komori K
  • Organizer: VEITH symposium Connecting The Vascular Community 46th Annual
  • Int'l Joint Research
• [Remarks] 名古屋大学 血管外科
  • URL: http://www.vascsurg.jp/
• [Remarks] 名古屋大学医学部医学系研究科・医学部医学科 血管外科学（第一外科学）
  • URL: https://www.med.nagoya-u.ac.jp/hospital/departments/vascular-s/