Single-cell transcriptomic analyses of cardiac immune cells reveal that Rel-driven CD72-positive macrophages induce cardiomyocyte injury

Cardiovasc Res. 2022 Mar 25;118(5):1303-1320. doi: 10.1093/cvr/cvab193.

Abstract

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.

Keywords: CD72; Heart failure; Macrophages; Rel; Single-cell RNA sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • Heart Injuries*
  • Humans
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • Monocytes
  • Myocytes, Cardiac*
  • Transcriptome

Substances

  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD72 protein, human