Physiological role of TRIC-B in heart hunction

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07313
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Yamazaki Daiju 国立医薬品食品衛生研究所, 薬理部, 室長 (40467428)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: TRICチャネル / 心臓 / 心機能 / Caトランジェント

Outline of Final Research Achievements

We generated cardiac-specific TRIC-B-KO (cKO) mice and investigated the function of TRIC-B in the heart. We found that cKO mice die 30-60 weeks of age. To confirm changes over time in the heart, we performed histopathological analysis at 12-40 weeks of age. We found that cKO mice had significantly higher blood troponin levels than wild-type mice > 12 weeks of age. cKO mice also showed marked cardiac fibrosis > 20 weeks of age and increased heart and lung weight > 30 weeks of age. Moreover, cKO mice showed decreased body weight, cardiomyocyte degeneration, and atrial thrombus at 40 weeks of age. Since these findings indicated heart failure-like pathology, echocardiographic examination of cardiac contractile function revealed a decrease in cardiac function after 30 weeks of age. These results suggest that at 12 weeks of age, there is already some abnormality in cKO cardiomyocytes.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

本研究により、小胞体カウンターイオンチャネルであるTRIC-Bの生物学的意義の解明にとどまらず、TRIC-Bが原因となる疾患の発症機序解明や治療薬開発など臨床的な応用も期待できる。