Interaction between renal tissue SGLT2 and the AT1R-NHE3 pathway as a mechanism for the progression of heart failure.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08102
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Mie University
• Principal Investigator: Dohi Kaoru 三重大学, 医学系研究科, 教授 (50422837)
• Co-Investigator(Kenkyū-buntansha): 岡本 隆二 三重大学, 医学部附属病院, 教授 (60378346) ; 片山 鑑 三重大学, 医学部附属病院, 准教授 (90742247) ; 伊藤 弘将 三重大学, 医学部附属病院, 寄附研究部門助教 (50898195)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 循環器

Outline of Final Research Achievements

Using an EAM rat model, we investigated the effects of SGLT2i under the inhibition of angiotensin II on inflammation in cardiac tissue across the normal group, EAM group, EAM/SGLT2i monotherapy group, EAM/ARB monotherapy group, and EAM/SGLT2i + ARB combination therapy group. The myocardial inflammation scoring, which reflects the degree of lymphocyte infiltration in myocardial tissue, showed no significant differences between the EAM group and the treatment groups. Furthermore, there were no significant differences in the mRNA expression levels of NLRP3, MMP-2, MMP-9, and MCP-1, known as inflammation markers, among the groups. On the other hand, in both the SGLT2i monotherapy group and the SGLT2i + ARB combination therapy group, a significant suppression of cardiac function decline was observed compared to the EAM group. Additionally, plasma troponin I levels tended to be lower in these groups compared to the EAM group, suggesting a cardioprotective effect of SGLT2i.

Free Research Field

心不全

Academic Significance and Societal Importance of the Research Achievements

HFrEF患者に対するSGLT2iは心不全の原因に関わらず心不全入院や腎機能障害の進展を抑制することが示されている。一方で、HFrEFに対する代表的な標準治療薬であるRAA系抑制薬との相互的な心・腎保護効果における関連性やその分子学機序は十分に検討されていない。また、心不全の進展課程において、炎症の重要性が明らかになりつつあり、EAMラットモデルを用いた研究により、SGLT2iとRAA系抑制薬の抗炎症に関する知見を得ることは今後の研究に新たな視点を見出すヒントになると考えられる。