A new mechanism of coronary spastic angina: Possible role of beta-arrestin

• Project/Area Number: 18K15875
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Hirosaki University
• Principal Investigator: Hanada Kenji 弘前大学, 医学研究科, 客員研究員 (90632993)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 冠攣縮性狭心症 / βアレスチン

Outline of Final Research Achievements

To elucidate the mechanism of coronary spastic angina, we focused on the role of beta-arrestin on vascular smooth muscle cells. The increase of intracellular calcium concentration in response to acetylcholine, an inducer of coronary spasm, was enhanced by beta-arrestin 1 knockdown (the concentration of intracellular calcium is commonly correlated with the strength of smooth muscle cell contraction). In contrast, overexpression of beta-arrestin 1 reduced the enhancement of intracellular calcium concentration in response to acetylcholine. Thus, beta-arrestin 1 may have inhibitory effect for coronary spasm.

Academic Significance and Societal Importance of the Research Achievements

冠攣縮性狭心症は日本人に多い疾患で、典型的には朝方の安静時胸痛を特徴とし、時に若年性の突然死の原因となる。冠拡張薬の内服により症状が改善することが多いが、少なからず難治例も存在し、対症療法であるため、内服薬を中断すると再発する。また、病因も未だ解明されていない。今回、我々は冠攣縮性狭心症の発症機序にβアレスチンが関与している可能性を明らかにした。この疾患におけるβアレスチンの役割が解明されることによって、将来的には新薬の開発の一助となる可能性がある。

Research Products

• [Presentation] β-Arrestin 1 Negatively Regulates Intracellular Calcium Concentration in Acetylcholine M3 Receptor: Its Possible Role in Coronary Spastic Angina (2019)
  • Author(s): 妹尾麻衣子、花田賢二、他
  • Organizer: 第８３回日本循環器学会学術集会