Elucidation of the role of canstatin, a cleaved fragment of type IV collagen, in the development of cardiac disease

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08028
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Kitasato University
• Principal Investigator: Okada Muneyoshi 北里大学, 獣医学部, 准教授 (30453509)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 薬理学 / 心疾患 / カンスタチン / 心筋梗塞 / 細胞死 / 心肥大 / 筋線維芽細胞 / カルシウムチャネル

Outline of Final Research Achievements

Canstatin is a cleaved fragment of type IV collagen α2 chain, which is a component of basement membrane surrounding cardiomyocytes. This project aimed to clarify the pathophysiological role and regulatory mechanism of canstatin in heart. It has been demonstrated that canstatin inhibits hypoxia-induced apoptosis in cardiomyoblasts and regulates cellular functions of myofibroblasts and ion channel activity of ventricular myocytes. It has been also revealed that canstatin exerts cardioprotective effects on experimental models of cardiac disease. Further, mechanism of decrease in canstatin expression in myocardial infarction was clarified.
This study suggested that canstatin is an endogenous bioactive molecule working cardioprotectively. Based on the results of this study, it is expected that development of novel strategies for cardiac disease treatment targeting canstatin will progress.

Free Research Field

循環薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究からカンスタチンが心保護的に働く内因性生理活性物質であることが示唆された。本研究成果を基盤として、カンスタチンを標的とした新たな心疾患治療戦略の開発が進むことが期待される。