Integrative functional analysis of CXCR7-associated inflammatory cells in the post-myocardial infarction remodeling

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16048
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Ishizuka Masato 東京大学, 医学部附属病院, 病院診療医(出向) (60897677)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: CXCR7 / 心筋梗塞

Outline of Final Research Achievements

I stimulated rat neonatal isolated cardiomyocytes with the specific agonist of CXCR7, TC14012, and analyzed the changes in gene expression using RNAseq. Although I observed changes in gene expression related to cellular cytoskeleton and mitochondrial metabolism, the number of genes showing significant changes was small, and I could not identify specific pathways through GO analysis. Unlike under ischemic conditions, this suggests that the effect on cardiomyocytes in a normal state is limited. Therefore, I am proceeding with experiments using a low-oxygen chamber to reproduce ischemic conditions such as myocardial infarction. Furthermore, in a mouse myocardial infarction model, I have identified temporal changes in gene expression related to apoptosis after myocardial infarction and am continuing the analysis.

Free Research Field

循環器学

Academic Significance and Societal Importance of the Research Achievements

CXCR7は、心筋梗塞後リモデリング形成過程において心保護的に働くことが示されたものの、CXCR7と共役するβアレスチンとERK以下の、細胞死に関わる経路は全くもって不明であった。今回、CXCR7が正常状態に比べて、より虚血下で作動することが示唆され、特にアポトーシス抑制に関わるシグナルとの関連が疑われた。更に条件検討を行い、より網羅的な解析を行うことで、CXCR7と細胞死を結びつけるより詳細なpathwayが解明され、心筋梗塞や心不全を治療するための創薬に繋がると考える。