A transient wave of Bhlhe41+ resident macrophages enables remodeling of the developing infarcted myocardium

• Published in: Cell reports (Cambridge) 2023-10, Vol.42 (10), p.113174-113174, Article 113174
• Main Authors: Xu, Yue, Jiang, Kai, Su, Fanghua, Deng, Ruhua, Cheng, Zhiyang, Wang, Dandan, Yu, Yong, Xiang, Yaozu
• Format: Article
• Language: English
• Subjects: Bhlhe41+ macrophages; cardiac remodeling; CP: Immunology; fibrosis; myocardial infarction
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.113174

The immune system plays a critical role during myocardial injury, contributing to repair and remodeling post myocardial infarction (MI). The myocardial infarct and border zone exhibit high heterogeneity, in turn leading to reconstructing macrophage subsets and specific functions. Here we use a combination of single-cell RNA sequencing, spatial transcriptomes, and reporter mice to characterize temporal-spatial dynamics of cardiac macrophage subtype in response to MI. We identify that transient appearance of monocyte-derived Bhlhe41+ Mφs in the “developing” infarct zone peaked at day 7, while other monocyte-derived macrophages are identified in “old” infarct zone. Functional characterization by co-culture of Bhlhe41+ Mφs with cardiomyocytes and fibroblasts or depletion of Bhlhe41+ Mφs unveils a crucial contribution of Bhlhe41+ Mφs in suppression of myofibroblast activation. This work highlights the importance of Bhlhe41+ Mφ phenotype and plasticity in preventing excessive fibrosis and limiting the expansion of developing infarct area. [Display omitted] •A novel subset of cardiac macrophages, termed Bhlhe41+ Mφs, ameliorates ischemic injury•Microenvironment post MI specifically activates Bhlhe41+ Mφs in the developing infarct zone•The Bhlhe41+ Mφs reduce myofibroblast activity and thus prevent excessive fibrosis Macrophages are highly plastic to respond to myocardial infarction, but the role of specific subset is not precisely characterized. Xu et al. reveal the transient appearance of monocyte-derived macrophage subpopulation (Bhlhe41+ Mφs) dominated in the “developing” infarct zone endowed with cardiac repair function, limiting the expansion of developing infarct area.