Developmental mechanism of cardiac macrophages

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K21311
• Project/Area Number (Other): 18H06208 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0902:General internal medicine and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Matsubara Takumi 東京大学, 医学部附属病院, 特任臨床医 (60824836)
• Project Period (FY): 2018-08-24 – 2022-03-31
• Keywords: 心臓マクロファージ / 分化

Outline of Final Research Achievements

We have determined that only 1% of the cells that make up the heart regulate cardiac function, and the Amphiregulin (Areg) which secreted by cardiac macrophages is essential for maintaining cardiac homeostasis. In the present study, we revealed that important signals in the differentiation of cardiac macrophages are β-stimulation by catecholamines and fatty acids.We revealed that fatty acids are involved in the maturation of macrophages, and Gpr65 is required for this maturation. Gpr65 knockout mice have a reduced number of cardiac macrophages per unit weight of the heart. Mice transplanted with Gpr65 bone marrow cells showed cardiac enlargement and reduced cardiac contraction compared to the wild type.
Elucidation of the differentiation mechanism of cardiac macrophages, which is essential for maintaining heart homeostasis, may reveal new target molecules for the treatment of heart failure.

Free Research Field

心臓マクロファージ

Academic Significance and Societal Importance of the Research Achievements

組織マクロファージの分化機構で明らかになっているものは少なく、特に心臓マクロファージについてはその分化機構の詳細についての検討は少ない。心臓マクロファージは心臓の恒常性維持に必須であり、その機能異常は心臓突然死や心不全に関連している。
心臓の恒常性維持に必須である心臓マクロファージの分化機構を明らかにすることで、マクロファージの機能異常への介入が可能になり、新たな心不全治療の標的分子が明らかになる可能性がある。