The elucidation of the molecular mechanisms of heart failure after myocardial infarction and the proposal of novel therapeutic targets for heart failure

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23800
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0801:Pharmaceutical sciences and related fields
• Research Institution: Osaka University
• Principal Investigator: Matsumoto Kotaro 大阪大学, 薬学研究科, 招へい研究員 (90849879)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 心不全 / 心筋梗塞 / 炎症関連免疫細胞

Outline of Final Research Achievements

Cardiac remodeling is positively and negatively regulated by inflammatory immune cells; however, the molecular mechanisms are not fully understood. In the present study, novel myeloid cells expressing TGF-β3 and Glycoprotein A Repetitions Predominant (GARP) were found by single cell RNA-sequencing. The expression of TGF-β3 and GARP was increased in murine hearts after myocardial infarction (MI). Moreover, anti-TGF-β3 antibody treatment suppressed cardiac dysfunction and adverse cardiac remodeling 14 days after MI. Therefore, the myeloid cells expressing TGF-β3 and GARP may play a crucial role in cardiac remodeling. Future studies will assess the role of TGF-β3 and GARP in myeloid cells in cardiac remodeling using cell specific knockout mice.

Free Research Field

分子心臓病学

Academic Significance and Societal Importance of the Research Achievements

心疾患は我が国の死因別死亡率の第2位を占める。また、超高齢社会を迎えた我が国では、心不全パンデミックと称されるように、心不全患者が急増している。現在の治療を以てしても、心不全は予後不良の病態であるため、新たな心不全発症予防法の確立が重要である。本研究では、心筋梗塞後の心不全発症過程に、これまで知られていなかった炎症関連免疫細胞が関与する可能性を見出した。本研究成果は、新たな心不全治療標的の提唱に繋がると期待される。