Ni, Shi-Hao, Xu, Jin-Dong, Sun, Shu-Ning, Li, Yue, Zhou, Zheng, Li, Huan, Liu, Xin, Deng, Jian-Ping, Huang, Yu-Sheng, Chen, Zi-Xin, Feng, Wen-Jun, Wang, Jia-Jia, Xian, Shao-Xiang, Yang, Zhong-Qi, Wang, Sheng, Wang, Ling-Jun, and Lu, Lu
Aims The goal of our study was to investigate the heterogeneity of cardiac macrophages (CMφs) in mice with transverse aortic constriction (TAC) via single-cell sequencing and identify a subset of macrophages associated with heart injury. Methods and results We selected all CMφs from CD45+ cells using single-cell mRNA sequencing data. Through dimension reduction, clustering, and enrichment analyses, CD72hi CMφs were identified as a subset of pro-inflammatory macrophages. The pseudo-time trajectory and ChIP-Seq analyses identified Rel as the key transcription factor that induces CD72hi CMφ differentiation. Rel KD and Rel−/− bone marrow chimaera mice subjected to TAC showed features of mitigated cardiac injury, including decreased levels of cytokines and ROS, which prohibited cardiomyocyte death. The transfer of adoptive Rel-overexpressing monocytes and CD72hi CMφ injection directly aggravated heart injury in the TAC model. The CD72hi macrophages also exerted pro-inflammatory and cardiac injury effects associated with myocardial infarction. In humans, patients with heart failure exhibit increased CD72hi CMφ levels following dilated cardiomyopathy and ischaemic cardiomyopathy. Conclusion Bone marrow-derived, Rel-mediated CD72hi macrophages play a pro-inflammatory role, induce cardiac injury and, thus, may serve as a therapeutic target for multiple cardiovascular diseases. [ABSTRACT FROM AUTHOR]