Investigation for the risk of early manifestations of atherosclerosis after the onset of Kawasaki disease

• Project/Area Number: 15K09646
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Ishikawa Takamichi 浜松医科大学, 医学部附属病院, 講師 (30402283)
• Co-Investigator(Kenkyū-buntansha): 岩島 覚 浜松医科大学, 医学部附属病院, 講師 (20362197)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 川崎病 / 酸化ストレス / 血管内皮障害 / 動脈硬化

Outline of Final Research Achievements

We compared the derivatives of reactive oxygen metabolites (ROM), flow-mediated dilatation (FMD),
and biological characteristics in a population of 50 children: 10 patients with KD and coronary artery lesions (CAL)(group 1), 15 KD patients without CAL (group 2), and 25 healthy age- and sex-matched children (group 3).Our study suggests that oxidative stress is strongly associated with endothelial dysfunction in early
childhood patients with KD. Furthermore, we found that the longer the fever duration, the higher the risk of oxidativestress-induced endothelial dysfunction in these children.

Academic Significance and Societal Importance of the Research Achievements

動脈硬化の発症・進展には血管内皮障害、炎症、酸化ストレスの3者による悪循環が関与していると考えられている。しかし川崎病発症後の若年小児に関して炎症マーカーや酸化ストレスを評価・検討した報告はこれまでにない。現状では冠動脈病変が存在しなければ発症後5年で川崎病患者のフォローアップを終了する施設が多いが、本研究結果により川崎病発症後の動脈硬化に対するリスク層別化、予防戦略、管理方法ならびに治療戦略を創生するための基盤の確立が大いに期待される。

Research Products

• [Journal Article] The association between oxidative stress and endothelial dysfunction in early childhood patients with Kawasaki disease. (2018)
  • Author(s): Ishikawa T, Seki K.
  • Journal Title: BMC Cardiovasc Disord. Volume: 18 Issue: 1 Pages: 30-37
  • DOI: 10.1186/s12872-018-0765-9
  • Peer Reviewed / Open Access
• [Journal Article] Closure time of ductus arteriosus after birth based on survival analysis. (2018)
  • Author(s): Iwashima S, Satake E, Uchiyama H, Seki K, Ishikawa T.
  • Journal Title: Early Hum Dev. Volume: 121 Pages: 37-43
  • DOI: 10.1016/j.earlhumdev.2018.05.003
  • Peer Reviewed
• [Journal Article] Hemodynamic assessment in a child with renovascular hypertension using time-resolved three-dimensional cine phase-contrast MRI. (2015)
  • Author(s): shikawa T, Takehara Y, Yamashita S, Iwashima S, Sugiyama M, Wakayama T, Johnson K, Wieben O, Sakahara H, Ogata T
  • Journal Title: J Magn Reson Imaging Volume: 41 Pages: 165-168
  • Peer Reviewed
• [Presentation] The Association Between Small For Gestational Age And Congenital Heart Disease As Assessed By Echocardiography In 6041 Consecutive Newborns. (2018)
  • Author(s): Ishikawa T, Seki K.
  • Organizer: American Heart Association’s Scientific Sessions, November 10-13, 2018, Chicago, IL, USA.
  • Int'l Joint Research
• [Presentation] Small for gestational ageと先天性心疾患. (2018)
  • Author(s): 石川貴充
  • Organizer: 第54回日本小児循環器学会総会・学術集会 2018年7月 横浜市(日本)
• [Presentation] The Association Between Oxidative Stress and Premature Atherosclerosis in Early Childhood Patients With Kawasaki Disease (2017)
  • Author(s): Takamichi Ishikawa
  • Organizer: American Heart Association’s Scientific Sessions 2017 in Anaheim, California
  • Int'l Joint Research
• [Presentation] 川崎病発症後5年以内における酸化ストレスと血管内皮障害との関連 (2017)
  • Author(s): 石川貴充
  • Organizer: 第53回日本小児循環器学会総会・学術集会 浜松