| Project/Area Number |
18H02810
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山崎 基生 宮崎大学, 医学部, 特任教授 (30796983)
永田 さやか 宮崎大学, 医学部, 助教 (00452920)
鶴田 敏博 宮崎大学, 医学部, 准教授 (10389570)
加藤 丈司 宮崎大学, フロンティア科学総合研究センター, 教授 (20274780)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | アドレノメデュリン（AM） / PEG化AM / AM誘導体 / 高血圧症 / 心不全 / 脳血管性認知症 / AM受容体 / ｃAMP / 非臨床試験 / cAMP |
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| Outline of Final Research Achievements |
Adrenomedullin (AM) is a possible drug for cardiovascular disorders. We have developed a PEGylated AM derivative (PEG-AM) for clinical application because AM has a short half-life in the blood. We assessed the in vitro and in vivo activities of PEG-AM. The PEG-AM activated the AM receptors, in the similar manner to those of native AM, and the addition of PEG did not influence the receptor selectivity. The acute hypotensive effect of PEG-AM was much weaker than AM after bolus injection in rats. However, single subcutaneous injection of PEG-AM inhibited blood pressure increase in spontaneously hypertensive rats which were loaded with high salt diet. In four-vessel occlusion model rats, which exhibit vascular dementia, a single subcutaneous injection of PEG-AM reduced the escape latency in the hidden platform test. PEG-AM is a possible candidate compound for the treatment of cardiovascular diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
アドレノメデュリン（AM）はわが国で発見された重要な生理活性ペプチドであり、循環器疾患治療薬として有望である。しかし、ペプチドであるため半減期が短く、経静脈持続投与が必要なため利便性が悪い。本研究では研究代表者が発明したPEG化AMの循環器疾患治療薬としての基礎的研究を行った。PEG化AMが慢性心不全・難治性高血圧や脳血管性認知症の治療薬として有望であることが明らかになった。PEG化AMが将来循環器疾患の治療薬として実用化されれば、高齢化社会でさらに増加する循環器疾患の制圧にもつながり、医学の発展ばかりでなく医療の発展にも貢献できるため社会的な意義も大きい。
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