Mechanisms of heart failure benefits from SGLT2 inhibitor using a single cardiomyocyte stretch system

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20886
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Asahikawa Medical College
• Principal Investigator: Chiba Yumiko 旭川医科大学, 医学部, 助教 (70835777)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: SGLT2阻害薬 / 心不全 / 酸化ストレス / ROS / 機械的負荷 / 伸展刺激 / SMIT1 / NOX2

Outline of Final Research Achievements

We found empagliflozin (EMPA) significantly suppresses acute stretch-induced ROS production in cardiomyocyte. Since SGLT2 is not expressed in the heart, we hypothesized that SMIT1, a member of the SGLT family, is involved in this phenomenon. We stimulated SMIT1 by administrating myoinositol and found that myoinositol induced ROS production, which is abolished by EMPA. From these results, we conclude that SGLT2 inhibitors suppress acute stretch-induced ROS production by inhibiting SMIT1 activity.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

SGLT2阻害薬は慢性心不全の治療薬として使用されているが、その心不全改善メカニズムの詳細は不明であった。本研究成果により、SGLT2阻害薬であるエンパグリフロジンは心筋細胞へ急性伸展刺激を与えたときに発生する酸化ストレスの一因である活性酸素種（ROS）の産生を抑制することがわかり、これか心不全改善効果の一端を担っていることが示唆された。