Development of novel antihypertensive therapy with tissue protection in renal and cardiovascular diseases through elucidation of MK-EETs blood pressure regulation mechanism

• Project/Area Number: 16K09609
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Nagoya University
• Principal Investigator: Kato sawako 名古屋大学, 医学系研究科, 特任講師 (80625757)
• Co-Investigator(Kenkyū-buntansha): 湯澤 由紀夫 藤田医科大学, 医学部, 教授 (00191479) ; 丸山 彰一 名古屋大学, 医学系研究科, 教授 (10362253) ; 小杉 智規 名古屋大学, 医学系研究科, 講師 (90584681)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: Midkine / 血管拡張因子 / EETs / midkine / 高血圧 / エポキシエイコサトリエン酸 / midline / ミッドカイン / 高血圧症 / 慢性腎臓病

Outline of Final Research Achievements

In a system aiming at deep observation of the living body using multiphoton confocal laser microscope A1R MP (Nikon), administration of epoxy eicosatrienoic acids (EETs) inhibitor and adenosine inhibitor, induced the vasoconstrictive action in Midkine (MK) deficient mice. The blood vessels were contracted and blood flow was decreased, as blood pressure increased. The blood flow rate was rising. On the other hand, when a nicotinic acetylcholine receptor inhibitor was administered to evaluate the sympathetic nervous system, blood pressure dropped in MK deficient mice, indicating an increase in blood flow. MK has been shown to regulate renal and blood pressure via a vasodilator.

Academic Significance and Societal Importance of the Research Achievements

高血圧症は腎硬化症を引き起こし、ひいては末期腎不全に至り、血液浄化療法を必要とする。現在の降圧剤は血管平滑筋に作用し、血管拡張作用を促すCa拮抗薬やRenin-angiotensin系阻害を促すACE阻害剤やARBといった薬剤が主流である。本研究では、血管拡張因子を介して血管拡張を調整する新規分子としてMidkineの血圧調整についてその有用性と根底にある機序を解明した。今後、新規降圧療法の一助となると考える。

Research Products

• [Journal Article] Efficacy of urinary midkine as a biomarker in patients with acute kidney injury. (2016)
  • Author(s): Hayashi H, Sato W, Kosugi T, Nishimura K, Sugiyama D, Asano N, Ikematsu S, Komori K, Nishiwaki K, Kadomatsu K, Matsuo S, Maruyama S, Yuzawa Y.
  • Journal Title: Clin Exp Nephrol Volume: Epub Issue: 4 Pages: 597-607
  • DOI: 10.1007/s10157-016-1318-0
  • NAID: 120006623838
  • Peer Reviewed