Selective loss of resident macrophage-derived insulin-like growth factor-1 abolishes adaptive cardiac growth to stress

Rysa Zaman, Homaira Hamidzada, Crystal Kantores, Anthony Wong, Sarah A. Dick, Yiming Wang, Abdul Momen, Laura Aronoff, Julia Lin, Babak Razani, Seema Mital, Filio Billia, Kory J. Lavine, Sara Nejat, Slava Epelman

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Hypertension affects one-third of the world's population, leading to cardiac dysfunction that is modulated by resident and recruited immune cells. Cardiomyocyte growth and increased cardiac mass are essential to withstand hypertensive stress; however, whether immune cells are involved in this compensatory cardioprotective process is unclear. In normotensive animals, single-cell transcriptomics of fate-mapped self-renewing cardiac resident macrophages (RMs) revealed transcriptionally diverse cell states with a core repertoire of reparative gene programs, including high expression of insulin-like growth factor-1 (Igf1). Hypertension drove selective in situ proliferation and transcriptional activation of some cardiac RM states, directly correlating with increased cardiomyocyte growth. During hypertension, inducible ablation of RMs or selective deletion of RM-derived Igf1 prevented adaptive cardiomyocyte growth, and cardiac mass failed to increase, which led to cardiac dysfunction. Single-cell transcriptomics identified a conserved IGF1-expressing macrophage subpopulation in human cardiomyopathy. Here we defined the absolute requirement of RM-produced IGF-1 in cardiac adaptation to hypertension.

Original languageEnglish
Pages (from-to)2057-2071.e6
JournalImmunity
Volume54
Issue number9
DOIs
StatePublished - Sep 14 2021

Keywords

  • IGF-1
  • cardiac
  • cardiomyocyte hypertrophy
  • fate mapping
  • heart failure
  • hypertension
  • macrophages
  • organ growth
  • resident macrophages
  • scRNA-seq

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