Clarification of vasculitis in Kawasaki disease; focusing on the endothelial microparticles

• Project/Area Number: 15K09686
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: University of Toyama
• Principal Investigator: Hirono Keiichi 富山大学, 附属病院, 助教 (80456384)
• Co-Investigator(Kenkyū-buntansha): 高崎 一朗 富山大学, 大学院理工学研究部(工学), 准教授 (00397176) ; 山本 誠士 富山大学, 大学院医学薬学研究部(医学), 助教 (10456361) ; 伊吹 圭二郎 富山大学, 附属病院, 医員 (20566096) ; 市田 蕗子 富山大学, 事務局, 学長補佐 (30223100) ; 小澤 綾佳 富山大学, 附属病院, 診療助手 (40596540)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 川崎病 / 血管内皮微小粒子 / 血管炎 / 血管内皮細胞 / 微少粒子

Outline of Final Research Achievements

EMPs could serve as a sensitive marker for characterizing the severity of endothelial damage and vasculitis in acute KD. Moreover, these specific miRs, hsa-miR-145-5p and hsa-miR-320a, may participate in modulation of inflammatory cytokine expression levels, and may contribute to pathogenesis of vasculitis in acute KD. Our novel findings might offer a new clinical approach for the treatment of KD. Further efforts are needed to develop the highly efficient molecular targeting therapies for KD.

Research Products

• [Int'l Joint Research] バルセロナ研究所(スペイン)
• [Int'l Joint Research] ミュンスター大学(ドイツ)
• [Int'l Joint Research] ミュンスター大学(ドイツ)
• [Journal Article] Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events. (2018)
  • Author(s): Miura M, Kobayashi T, Fukaza R et al
  • Journal Title: JAMA Pediatr Volume: 5 Issue: 5 Pages: 180030-180030
  • DOI: 10.1001/jamapediatrics.2018.0030
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] MicroRNA-145-5p and microRNA-320a encapsulated in endothelial microparticles contribute to the progression of vasculitis in acute Kawasaki Disease. (2018)
  • Author(s): Nakaoka H, Hirono K, Yamamoto S, Takasaki I, Takahashi K, Kinoshita K, Takasaki A, Nishida N, Okabe M, Ce W, Miyao N, Saito K, Ibuki K, Ozawa S, Adachi Y, Ichida F.
  • Journal Title: Sci Rep. Volume: 8 Issue: 1 Pages: 1016-1023
  • DOI: 10.1038/s41598-018-19310-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 5.Infliximab for the Treatment of Refractory Kawasaki Disease: A Nationwide Survey in Japan. (2017)
  • Author(s): Masuda H, Kobayashi T, Hachiya A, Nakashima Y, Shimizu H, Nozawa T, Ogihara Y, Ito S, Takatsuki S, Katsumata N, Suzuki Y, Takenaka S, Hirono K, Kobayashi T, Suzuki H, Suganuma E, Takahashi K, Saji T
  • Journal Title: J Pediatr. Volume: - Pages: 115-120.e3
  • DOI: 10.1016/j.jpeds.2017.10.013
  • Peer Reviewed / Open Access
• [Journal Article] Evidences of endothelial damage in acute stage. (2016)
  • Author(s): Hirono K and Ichida F
  • Journal Title: Kawasaki Disease: Current Understanding of Mechanism and Evidence-based Treatment. Springer Japan Volume: - Pages: 335-340
  • Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Anomalous origin of the right coronary artery evaluated with multidetector computed tomography and its clinical relevance. (2016)
  • Author(s): Hirono K, Hata Y, Miyao N, Nakaoka H, Saito K, Ibuki K, Watanabe K, Ozawa S, Higuma T, Yoshimura N, Nishida N, Ichida F
  • Journal Title: J Cardiol Volume: 68 Issue: 3 Pages: 196-201
  • DOI: 10.1016/j.jjcc.2015.12.010
  • Peer Reviewed
• [Journal Article] MicroRNA-93 may control vascular endothelial growth factor A in circulating peripheral blood mononuclear cells in acute Kawasaki Disease (2016)
  • Author(s): Saito K, Nakaoka H, Takasaki I, Hirono K, Yamamoto S, Kinoshita K, Miyao N, Ibuki K, Ozawa S, Watanabe K, Bowles NE, Ichida F
  • Journal Title: Pediatr Res Volume: 80 Issue: 3 Pages: 425-432
  • DOI: 10.1038/pr.2016.93
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] iPSC-derived cardiomyocytes reveal abnormal TGF-β (2016)
  • Author(s): Kodo K, Ong SG, Jahanbani F, Termglinchan V, Hirono K, InanlooRahatloo K,
  • Journal Title: Nat Cell Biol. Volume: 18 Issue: 10 Pages: 1031-42
  • DOI: 10.1038/ncb3411
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Postmortem genetic analysis of sudden unexplained death syndrome under 50 years of age: A next-generation sequencing study. (2016)
  • Author(s): Hata Y, Kinoshita K, Mizumaki K, Yamaguchi Y, Hirono K, Ichida F, Takasaki A, Mori H, Nishida N.
  • Journal Title: Heart Rhythm. Volume: 13 Issue: 7 Pages: 1544-1551
  • DOI: 10.1016/j.hrthm.2016.03.038
  • Peer Reviewed / Open Access
• [Journal Article] Utility of TNF-α as a Biomarker and the Possibility of anti-TNF-α Therapy for Kawasaki Diseases. (2015)
  • Author(s): Hirono K and Ichida F.
  • Journal Title: Pediat Therapeut Volume: 5 Pages: 257-261
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Left ventricular noncompaction (2017)
  • Author(s): Hirono K, Hata Y, Ichida F, et al.
  • Organizer: 第81回日本循環器学会
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
• [Presentation] Postmortem genetic analysis for sudden unexpected death; the current status and future perspectives- (2017)
  • Author(s): Hata Y, Hirono K, and Ichida F, et al.
  • Organizer: 第81回日本循環器学会
  • Place of Presentation: 金沢
  • Year and Date: 2017-03-17
• [Presentation] 多発性の巨大冠動脈瘤と末梢動脈瘤で遠隔期に発見された不全型川崎病について (2017)
  • Author(s): 宮尾成明、岡部真子、齋藤和由、小澤綾佳、廣野恵一
  • Organizer: 第26回小児循環器病カンファレンス
• [Presentation] 冠動脈瘤をともなう川崎病患者のレジストリ研究 (2017)
  • Author(s): 三浦 大，鮎澤 衛，池田 和幸，加藤 太一，小林 徹，塩野 淳子，須田 憲治，津田 悦子，沼野 藤人，廣野 恵一，深澤 隆治，前田 潤，三谷 義英，脇 研自
  • Organizer: 2017年度日本小児科学会
• [Presentation] 川崎病罹患後にペースメーカー心室閾値の上昇を認めた洞不全症候群の1例 (2017)
  • Author(s): 岡部真子、宮尾成明、仲岡英幸、齋藤和由、小澤綾佳、廣野恵一、市田蕗子、池野友基、青木正哉、芳村直樹
  • Organizer: 2017年度日本小児循環器学会
• [Presentation] 川崎病バイオマーカーのエビデンス分類 (2017)
  • Author(s): 勝部康弘、今中恭子、武田充人、阿部淳、小林徹、益田博司、大熊喜彰、深澤隆治、高月晋一、加藤太一、三谷義英、廣野恵一、池田和幸、吉兼由佳子、須田憲治、永田弾、山村健一郎、佐地勉
  • Organizer: 第37回 日本川崎病学会・学術集会
• [Presentation] 腫瘍壊死因子による免疫グロブリン大量療法への不応例予測の可否 －多施設共同研究－ (2017)
  • Author(s): 勝部康弘、今中恭子、武田充人、阿部淳、小林徹、益田博司、大熊喜彰、深澤隆治、高月晋一、加藤太一、三谷義英、廣野恵一、池田和幸、吉兼由佳子、須田憲治、永田弾、山村健一郎、佐地勉
  • Organizer: 第37回 日本川崎病学会・学術集会
• [Presentation] 冠動脈瘤をともなう川崎病患者のレジストリ研究計画 (2017)
  • Author(s): 三浦 大，鮎澤 衛，池田 和幸，加藤 太一，小林 徹，塩野 淳子，須田 憲治，津田 悦子，沼野 藤人，廣野 恵一，深澤 隆治，前田 潤，三谷 義英，脇 研自
  • Organizer: 第37回 日本川崎病学会・学術集会
• [Presentation] 26.バイオフィルム制御薬クラリスロマイシンの川崎病再燃抑制効果に関する検証的試験 -多施設共同ランダム化比較第３相試験- (UMIN000024311) (2017)
  • Author(s): 古野憲司、名西悦郎、小野山さがの、水野由美、神園淳司、中谷圭吾、大野拓郎、脇研自、今井祐喜、篠木敏彦、西村真二、土井大人、波多江健、長友雄作、大淵典子、菅沼栄介、市田蕗子、宮本辰樹、篠原修、吉田史則、山口賢一郎、加藤太一、中島康貴、西尾壽乘、倉岡彩子、原寿郎
  • Organizer: 第37回 日本川崎病学会・学術集会
• [Presentation] 好中球/リンパ球比、血小板/リンパ球比によるIVIG不応の予測に関する多施設共同研究 (2017)
  • Author(s): 金井貴志、竹下誠一郎、川村陽一、木下恵司、中谷圭吾、岩島覚、滝澤裕司、廣野恵一、森一越、吉田裕輔、野々山恵章
  • Organizer: 第37回 日本川崎病学会・学術集会
• [Presentation] 川崎病急性期におけるlong noncoding RNAの発現解析 (2017)
  • Author(s): 岡部真子、廣野恵一、宮尾成明、仲岡英幸、齋藤和由、小澤綾佳、市田蕗子、木下耕史、高崎一朗
  • Organizer: 第37回 日本川崎病学会・学術集会
• [Presentation] Long-term prognosis of the pediatric patients with Left Ventricular Noncompaction. (2016)
  • Author(s): Hirono K, Hata Y, Ichida F, et al.
  • Organizer: 2nd International Congress of Cardiomyopathies and Heart Failure 2016
  • Place of Presentation: 京都
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] Endothelial microparticles modulate vasculitis during the acute phase of Kawasaki Disease (2016)
  • Author(s): Nakaoka H, Hirono K, Takasaki I, Yamamoto S, Ichida F, et al.
  • Organizer: The 89th Scientific sessions of AHA 2016
  • Place of Presentation: ニューオーリンズ、米国
  • Year and Date: 2016-11-15
  • Int'l Joint Research
• [Presentation] 川崎病急性期における血管内皮細胞由来の血管微小粒子(EMPs)の役割 (2016)
  • Author(s): 仲岡英幸、廣野恵一、岡部真子、宮尾成明、伊吹圭二郞、齋藤和由、小澤綾佳、市田蕗子
  • Organizer: 第36回日本川崎病学会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-01
• [Presentation] Clinical Features and Prognosis of Pediatic Patients with Left Ventricular Noncompaction (2016)
  • Author(s): Hirono K, Hata Y, Ichida F, et al.
  • Organizer: European society for cardiology congress 2016
  • Place of Presentation: ローマ、イタリア
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] Increased circulating endothelial microparticles in the acute phase of Kawasaki Disease. (2015)
  • Author(s): Hideyuki Nakaoka, Keiichi Hirono, Keijiro Ibuki, Sayaka Ozawa, Fukiko Ichida.
  • Organizer: The 88th Scientific sessions of AHA 2015, Orlando, Florida,
  • Place of Presentation: 米国フロリダ
  • Year and Date: 2015-11-09
  • Int'l Joint Research
• [Presentation] 川崎病急性期における血管内皮細胞由来の血管微小粒子(EMPs)の役割 (2015)
  • Author(s): 仲岡 英幸, 伊吹 圭二郎, 小澤 綾佳, 廣野 恵一, 足立 雄一, 市田 蕗子
  • Organizer: 第３５回日本川崎病学会、鹿児島
  • Place of Presentation: 鹿児島
  • Year and Date: 2015-10-09
• [Presentation] 川崎病急性期における血管内皮細胞由来の血管微小粒子(EMPs)の役割 (2015)
  • Author(s): 仲岡 英幸, 伊吹 圭二郎, 小澤 綾佳, 廣野 恵一, 足立 雄一, 市田 蕗子
  • Organizer: 第51回日本小児循環器学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-17
• [Book] 適切な学校心臓検診－見逃してはいけないポイントと管理 (2018)
  • Author(s): 廣野恵一、市田蕗子
  • Publisher: 週刊日本医事新報、日本医事新法社
• [Book] 川崎病の病因研究概論 (2017)
  • Author(s): 廣野恵一、市田蕗子
  • Publisher: 日本川崎病学会病因検討小委員会編 日本川崎病各界事務局
• [Book] 川崎病のすべて：インフリキシマブ療法 (2015)
  • Author(s): 廣野恵一、市田蕗子
  • Total Pages: 4
  • Publisher: 中山書店