Molecular mechanisms of cardiac hypertrophy/heart failure by Ca2+ transporter candidates and its application to drug discovery

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08610
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Fukuoka University
• Principal Investigator: Iwamoto Takahiro 福岡大学, 医学部, 教授 (20300973)
• Co-Investigator(Kenkyū-buntansha): 田頭 秀章 福岡大学, 医学部, 講師 (90735028)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: イオン輸送体 / 心不全 / 心肥大 / 病態モデル動物

Outline of Final Research Achievements

Solute carrier (SLC) transporters are membrane proteins that facilitate the transport of substrates across biological membranes. We confirmed that the targeted SLC transporter can transport Ca2+, using mammalian cell expression system. Interestingly, cardiac-specific transgenic mice of the target SLC transporter exhibited cardiac hypertrophy, reduced cardiac function, and early sudden death. Furthermore, we observed abnormal Ca2+ transients in cultured cardiac myocytes from the cardiac-specific transgenic mice. These results suggest that upregulation of the targeted SLC transporter may induce cardiac hypertrophy/heart failure. We established the screening system for the specific inhibitors, which might be useful therapeutically.

Free Research Field

分子薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究では、SLCトランスポーター群の中から新規なCa2+輸送体（標的SLC輸送体分子）を見出した。この遺伝子改変マウスを用いた病態生理学的解析から、標的SLC輸送体分子は、心肥大・心不全の誘発因子である可能性が示唆された。本研究成果は、心肥大・心不全の病態解明に貢献するのみならず、新たな心不全治療薬の開発に繋がることが期待される。