Elucidation of the mechanism of imbalance between PlGF and sFlt-1 in chronic kidney disease

• Project/Area Number: 18K15857
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Nara Medical University
• Principal Investigator: NAKADA YASUKI 奈良県立医科大学, 医学部附属病院, 研究員 (70812379)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 心腎連関 / 胎盤増殖因子 / 心血管疾患

Outline of Final Research Achievements

In patients with chronic kidney disease, cardiovascular disease has a significant impact on prognosis. Conversely, in patients with heart disease, renal dysfunction worsens the prognosis. One of the mechanisms of cardiorenal syndrome is imbalanced expression between placental growth factor (PlGF) that promotes atherosclerosis and soluble Flt-1 (sFlt-1) as an antagonist of PlGF.
We showed that AST-120, an oral carbon absorbent, protects against the progression of atherosclerosis in a mouse chronic renal failure model by preserving sFlt-1 expression levels. In this study, we also reported that value of PlGF as a predictor of adverse events during the acute phase of acute heart failure.

Academic Significance and Societal Importance of the Research Achievements

実臨床において，心血管疾患を有している患者の多くで腎機能が低下し，それらの症例においては特に治療に難渋している．心腎連関の概念は近年注目されており，その機序の解明とともに新規の治療薬を開発することが重要な意味を持っている．今回，既存薬剤が慢性腎臓病患者の抗動脈硬化作用に効果がある可能性を示したことは意味のあることである．また，入院時の胎盤増殖因子(PlGF)の値が予後予測につながることから，現場での治療選択に役立つことが考えられる．

Research Products

• [Journal Article] Value of Placental Growth Factor as a Predictor of Adverse Events During the Acute Phase of Acute Decompensated Heart Failure (2019)
  • Author(s): Nakada Y, Kawakami R, Matsui M, Ueda T, Nakano T, Nakagawa H, Nishida T, Onoue K, Soeda T, Okayama S, Watanabe M, Okura H, Saito Y.
  • Journal Title: Circulation Journal Volume: 83 Issue: 2 Pages: 395-400
  • DOI: 10.1253/circj.CJ-18-0523
  • NAID: 130007557048
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2019-01-25
  • Peer Reviewed / Open Access
• [Journal Article] AST-120, an Oral Carbon Absorbent, Protects against the Progression of Atherosclerosis in a Mouse Chronic Renal Failure Model by Preserving sFlt-1 Expression Levels. (2019)
  • Author(s): Nakada Y, Onoue K, Nakano T, Ishihara S, Kumazawa T, Nakagawa H, Ueda T, Nishida T, Soeda T, Okayama S, Watanabe M, Kawakami R, Saito Y.
  • Journal Title: Sci Rep. Volume: 9 Issue: 1 Pages: 15571-15571
  • DOI: 10.1038/s41598-019-51292-9
  • Peer Reviewed / Open Access
• [Remarks] 奈良医大循環器内科ホームページ
  • URL: http://www.naramed-u.ac.jp/~1int/