Cardiovascular research · 2022
Single-cell transcriptomic analyses of cardiac immune cells reveal that Rel-driven CD72-positive macrophages induce cardiomyocyte injury.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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, Lu Lu
Аннотация
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.
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.