Development of new therapy of cardiovascular disease utilizing specificity of biologically active peptide hormones

• Project/Area Number: 22790891
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Endocrinology
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: TOKUDOME Takeshi 独立行政法人国立循環器病研究センター, 生化学部, 室長 (00443474)
• Research Collaborator: SCHWENKE Daryl O. オタゴ大学, 教官 ; MAO Yuanjie 独立行政法人国立循環器病研究センター, 生化学部, 流動研究員
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 内分泌学 / グレリン / ナトリウム利尿ペプチド / 心筋梗塞 / 末梢動脈閉塞性疾患

Research Abstract

We recently published that ghrelin(an orexigenic peptide) administration was able to improve malignant arrhythmia-induced mortality in acute myocardial infarction. The present study demonstrated that one dose of ghrelin improves death rate in acute phase and also prevents cardiac remodeling in myocardial infarction. Furthermore, also demonstrated that endogenous ghrelin suppressed arrhythmia-induced death through inhibition of sympathetic nerve activity and activation of parasympathetic nerve activity in acute myocardial infarcti on. These findings suggest potential usefulness of ghrelin as a therapeutic agent in myocardial infarction.

Research Products

• [Journal Article] Natriuretic peptide receptor guanylyl cyclase-A protects podocytes from aldosterone-induced glomerular injury (2012)
  • Author(s): Ogawa Y, Mukoyama M, Yokoi H, Kasahara M, Mori K, Kato Y, Kuwabara T, Imamaki H, Kawanishi T, Koga K, Ishii A, Tokudome T, Kishimoto I, Sugawara A, Nakao K
  • Journal Title: J Am Soc Nephrol Volume: 23:1198-1209 Issue: 7 Pages: 1198-1209
  • DOI: 10.1681/asn.2011100985
  • Peer Reviewed
• [Journal Article] Ghrelin Prevents Incidence of Malignant Arrhythmia after Acute Myocardial Infarction through Vagal Afferent Nerves (2012)
  • Author(s): Mao Y, Tokudome T, Otani K, Kishimoto I, Nakanishi M, Hosoda H, Miyazato M, Kangawa K
  • Journal Title: Endocrinology Volume: (in press) Issue: 7 Pages: 3426-3434
  • DOI: 10.1210/en.2012-1065
  • Peer Reviewed
• [Journal Article] One dose of ghrelin prevents the acute and sustained increase in cardiac sympathetic tone after myocardial infarction (2012)
  • Author(s): Schwenke DO, Tokudome T, Kishimoto I, Horio T, Cragg PA, Shirai M, Kangawa K
  • Journal Title: Endocrinology Volume: 153(5) Issue: 5 Pages: 2436-2443
  • DOI: 10.1210/en.2011-2057
  • Peer Reviewed
• [Journal Article] The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice (2012)
  • Author(s): Fukuhara S, et al
  • Journal Title: J Clin Invest Volume: (In press)(未定) Issue: 4 Pages: 1416-1426
  • DOI: 10.1172/jci60746
  • Peer Reviewed
• [Journal Article] Ghrelin and cardiovascular diseases (2012)
  • Author(s): Kishimoto I, Tokudome T, Hosoda H, Miyazato M, Kangawa K
  • Journal Title: J Cardiology Volume: 59 Issue: 1 Pages: 8-13
  • DOI: 10.1016/j.jjcc.2011.11.002
  • NAID: 10019807283
  • Peer Reviewed
• [Journal Article] Centrally administered ghrelin activates cardiac vasal nerve in anesthetized rabbits (2011)
  • Author(s): Shimizu S, Akiyama T, Kawada T, Sonobe T, Kamiya A, Shishido T, Tokudome T, Hosoda H, Shirai M, Kangawa K, Sugimachi M
  • Journal Title: Auton Neurosci Volume: 162 Issue: 1-2 Pages: 60-65
  • DOI: 10.1016/j.autneu.2011.04.001
  • Peer Reviewed
• [Journal Article] Interleukin-6 as an independent predictor of future cardiovascular events in high-risk Japanese patients : comparison with C-reactive protein (2011)
  • Author(s): Nishida H, Horio T, Suzuki Y, Iwashima Y, Tokudome T, Yo shihara F, Nakamura S, Kawano Y
  • Journal Title: Cytokine Volume: 53(3) Issue: 3 Pages: 342-346
  • DOI: 10.1016/j.cyto.2010.12.005
  • Peer Reviewed
• [Journal Article] 内因性ナトリウム利尿ペプチドの虚血組織血管新生促進作用 (2011)
  • Author(s): 徳留健、岸本一郎、寒川賢治
  • Journal Title: 治療 Volume: 93(4) Pages: 686-688
  • NAID: 40018739233
  • Peer Reviewed
• [Journal Article] ナトリウム利尿ペプチドと肥満・インスリン抵抗性 (2011)
  • Author(s): 岸本一郎、徳留健、槇野久士、寒川賢治
  • Journal Title: 実験医学増刊 Volume: 29(5) Pages: 194-201
• [Journal Article] Natriuretic peptide system : an overview of studies using genetically engineered animal models (2011)
  • Author(s): Kishimoto I, Tokudome T, Nakao K and Kangawa K
  • Journal Title: FEBS Journal Volume: 278 Issue: 11 Pages: 1830-1841
  • DOI: 10.1111/j.1742-4658.2011.08116.x
  • Peer Reviewed
• [Journal Article] Interleukin-6 as an independent predictor of future cardiovascular events in high-risk Japanese patients : Comparison with C-reactive protein. (2011)
  • Author(s): Nishida H, et al.
  • Journal Title: Cytokine Volume: 53(3) Pages: 342-346
  • Peer Reviewed
• [Journal Article] Chronic kidney disease as an independent risk factor for new-onset atrial fibrillation in hypertensive patients (2010)
  • Author(s): Horio T, Iwashima Y, Kamide K, Tokudome T, Yoshihara F, Nakamura S, Kawano Y
  • Journal Title: J Hypertnes Volume: 28(8) Issue: 8 Pages: 1738-1744
  • DOI: 10.1097/hjh.0b013e32833a7dfe
  • Peer Reviewed
• [Journal Article] Association of insulin-like growth factor-1 receptor gene polymorphisms with left ventricular mass and geometry in essential hypertension (2010)
  • Author(s): Hori T, Kamide K, Takiuchi S. Yoshii M, Miwa Y, Matayoshi T, Yoshihara F, Nakamura S, Tokudome T, Miyata T, Kawano Y
  • Journal Title: J Hum Hypertens Volume: 24(5) Issue: 5 Pages: 320-326
  • DOI: 10.1038/jhh.2009.73
  • Peer Reviewed
• [Journal Article] Spring-8高輝度放射光を用いた小動物の心臓・血管機能の画像解析 (2010)
  • Author(s): 白井幹康、James Pearson, Daryl Schwenke,曽野部崇、藤井豊、吉本光佐、徳留健、清水壽一郎、寒川賢治、梅谷啓二、八木直人
  • Journal Title: 循環器研究の進歩 Volume: 30(1) Pages: 70-82
• [Journal Article] 内因性ナトリウム利尿ペプチドの虚血組織血管新生における役割 (2010)
  • Author(s): 徳留健、岸本一郎、寒川賢治
  • Journal Title: 脈管学 Volume: 50(2) Pages: 169-174
  • NAID: 10026911904
  • Peer Reviewed
• [Journal Article] Association of insulin-like growth factor-1 receptor gene polymorphisms with left ventricular mass and geometry in essential hypertension. (2010)
  • Author(s): Horio T, et al.
  • Journal Title: Journal of Human Hypertension Volume: 24(5) Pages: 320-326
  • Peer Reviewed
• [Journal Article] Chronic kidney disease as an independent risk factor for new-onset atrial fibrillation in patients with essential hypertension. (2010)
  • Author(s): Horio T, et al.
  • Journal Title: Journal of Hypertension Volume: 28(8) Pages: 1738-1744
  • Peer Reviewed
• [Presentation] 心脈管作動物質に関連した、次世代研究者による今後の研究展開 (2012)
  • Author(s): 徳留健
  • Organizer: 第41回日本心脈管作動物質学会物質学会
  • Place of Presentation: 秋田
  • Year and Date: 2012-02-11
• [Presentation] 心血管病を内分泌・代謝面から考察する (2011)
  • Author(s): 徳留健
  • Organizer: 察する第84回日本内分泌学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2011-04-22
• [Presentation] 内因性ナトリウム利尿ペプチドの心血管保護作用 (2011)
  • Author(s): 徳留健
  • Organizer: 第84回日本内分泌学会学術総会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2011-04-22
• [Presentation] 血管恒常性維持におけるANP・BNPの多彩な作用 (2011)
  • Author(s): 徳留健
  • Organizer: 第15回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 大阪
• [Presentation] Regulator of G-protein signaling subtype 4 mediates anti-hypertrophic effect of locally secreted natriuretic peptides in the heart. (2010)
  • Author(s): 徳留健
  • Organizer: The XX World Congress of the International Society for Heart Research
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2010-05-14
• [Presentation] Regulator of G-protein signaling subtype 4 mediates anti-hypertrophic effect of locally secreted natriuretic peptides in the heart (2010)
  • Author(s): 徳留健
  • Organizer: XX^<th> World Congress International Society for Heart Research
  • Place of Presentation: 京都
• [Remarks]
  • URL: http://www.ncvc.go.jp/res/divisions/biochemistry/index.html