New treatment for left ventricular diastolic failure

• Project/Area Number: 25461057
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Tottori University
• Principal Investigator: Ogino Kazuhide 鳥取大学, 医学部附属病院, 准教授 (70294311)
• Co-Investigator(Renkei-kenkyūsha): HISATOME Ichiro 鳥取大学, 医学(系)研究科(研究院), 教授 (60211504)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 心不全 / 拡張不全 / インスリン抵抗性 / アルドステロン / 高血圧

Outline of Final Research Achievements

We evaluated the effects of drug therapy on insulin resistance and purine-uric acid metabolism in heart failure, and discussed the possibility of new treatment of heart failure.　We induced ischemia-reperfusion injury using AMP deaminase deficient mouse and evaluated the mechanism and the relationship between heart failure and purine-uric acid metabolism. In addition, we evaluated the effects of an aldosterone antagonist and a loop diuretic on insulin resistance and cardiac function as well as fibrosis markers and inflammation markers in patients with heart failure.
From these studies, purine-uric metabolism and insulin resistance might be targets for new treatments of heart failure.

Research Products

• [Journal Article] Effects of Uric Acid on the NO Production of HUVECs and its Restoration by Urate Lowering Agents. (2016)
  • Author(s): Mishima M, Anzai N, et al.
  • Journal Title: Drug Res Volume: 66 Issue: 05 Pages: 270-274
  • DOI: 10.1055/s-0035-1569405
  • Peer Reviewed
• [Journal Article] Effect of Antihypertensive Drugs on Uric Acid Metabolism in Patients with Hypertension: Cross-Sectional Cohort Study. (2016)
  • Author(s): Ueno S, Hamada T, Taniguchi S, Ohtani N, Miyazaki S, Mizuta E, Ohtahara A, Ogino K, Yoshida A, Kuwabara M, Yoshida K, Ninomiya H, Kotake H, Taufiq F, Yamamoto K, Hisatome I
  • Journal Title: Drug Res (Stuttg) Volume: 66 Pages: 628-632
  • Peer Reviewed
• [Journal Article] Depletion of Uric Acid Due to SLC22A12 (URAT1) Loss-of-Function Mutation Causes Endothelial Dysfunction in Hypouricemia (2015)
  • Author(s): Sugihara S, Hisatome I, Kuwabara M, Niwa K, Maharani N, Kato M, Ogino K, Hamada T, Ninomiya H, Higashi Y, Ichida K, Yamamoto K
  • Journal Title: Circulation Journal Volume: 79 Issue: 5 Pages: 1125-1132
  • DOI: 10.1253/circj.CJ-14-1267
  • NAID: 130005066259
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] <b>Adipose stem cell sheets improved cardiac function in the rat myocardial infarction, but did not alter cardiac contractile responses to β-adrenergic stim</b><b>ulation </b> (2015)
  • Author(s): Otsuki Y, Nakamura Y, Harada S, Yamamoto Y, Ogino K, Morikawa K, Ninomiya H, Miyagawa S, Sawa Y, Hisatome I, Nishimura M.
  • Journal Title: Biomedical Research Volume: 36 Issue: 1 Pages: 11-19
  • DOI: 10.2220/biomedres.36.11
  • NAID: 130004903877
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access
• [Journal Article] Spironolactone, not furosemide, improved insulin resistance in patients with chronic heart failure (2014)
  • Author(s): Ogino K, Kinugasa Y, Kato M, Yamamoto K, Hisatome I, Anker SD, Doehner W
  • Journal Title: Int J Cardiol Volume: 171 Issue: 3 Pages: 398-403
  • DOI: 10.1016/j.ijcard.2013.12.039
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Losartan/hydrochlorothiazide combination therapy improved left ventricular diastolic dysfunction in patients with hypertension in comparison with a high-dose therapy of losartan (2016)
  • Author(s): Ogino K, Kinugasa Y, Kato M, Hisatome I, Yamamoto K
  • Organizer: American Society of Hypertension 2016
  • Place of Presentation: Hilton Hotel, New York, USA
  • Int'l Joint Research
• [Presentation] Uric AcidLowering Treatment in Patients with Left Ventricular Diastolic (2015)
  • Author(s): Ogino K
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府，北区）
  • Year and Date: 2015-04-24