2020 Fiscal Year Final Research Report

Basic study of novel adrenomedullin derivatives to develop as a pharmaceutical drug of cardiovascular diseases

Research Project

PDF

Project/Area Number	18H02810
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 53020:Cardiology-related
Research Institution	University of Miyazaki
Principal Investigator	KITAMURA KAZUO 宮崎大学, 医学部, 教授 (50204912)
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)
Project Period (FY)	2018-04-01 – 2021-03-31
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
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.
Free Research Field	循環器内科
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。