Exploring a novel therapeutic agent for myxomatous mitral valve disease: basic studies focusing on Metformin

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15683
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Kitasato University
• Principal Investigator: Kameshima Satoshi 北里大学, 獣医学部, 講師 (80826363)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 変性性僧帽弁疾患 / 犬 / メトホルミン / トランスフォーミング増殖因子β / 骨形成タンパク質

Outline of Final Research Achievements

Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs. Mitral valvular thickening associated with increased expression of transforming growth factor (TGF)β superfamily members including TGFβ and bone morphogenetic protein (BMP) can cause MMVD. However, no therapeutic agent inhibits the development of valvular thickening. While metformin, an oral medication prescribed for type 2 diabetes, is reported to have inhibitory role against the differentiating effects of TGFβ and BMP, its effect on mitral valvular thickening is unknown. The aim of this study was to explore it. In rat valvular interstitial cells, metformin inhibited TGFβ- or BMP-induced activation of the signaling molecules and increase in the expression of differentiation marker proteins including α-smooth muscle actin and alkaline phosphatase. Moreover, metformin decreased TGFβ-induced valvular thickening of isolated rat mitral valves.

Free Research Field

獣医循環器学

Academic Significance and Societal Importance of the Research Achievements

本研究によりメトホルミンがTGFβおよびBMPによるラット僧帽弁膜の変性を抑制する可能性が示された。将来的には、上述した作用の詳細なメカニズムの解明とイヌ僧帽弁組織を用いた検討を経て、自然発症MMVD罹患動物の病態に及ぼすメトホルミンの影響を調査する予定である。メトホルミンが弁膜変性の悪化を防ぐ可能性を示すことができれば、既存薬とは異なる薬効を有する新たなMMVD治療薬となるかもしれない。