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Updated: Aug 2, 2026
Isolation of Macrophage Subsets and Stromal Cells from Human and Mouse Myocardial Specimens
Published on: December 17, 2019
Selective loss of resident macrophage-derived insulin-like growth factor-1 abolishes adaptive cardiac growth to
Rysa Zaman1, Homaira Hamidzada1, Crystal Kantores2
1Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada; Ted Rogers Centre for Heart Research, Toronto, ON, Canada; Department of Immunology, University of Toronto, Toronto, ON, Canada.
Insights
Resident cardiac macrophages are crucial for adapting to hypertension. Their insulin-like growth factor-1 (IGF-1) production drives cardiomyocyte growth, maintaining cardiac mass and function under stress.
Area of Science:
- Cardiovascular Biology
- Immunology
- Macrophage Biology
Background:
- Hypertension impacts a third of the global population, often causing cardiac dysfunction.
- The role of immune cells, particularly cardiac resident macrophages (RMs), in the heart's adaptive response to hypertension is not fully understood.
Purpose of the Study:
- To investigate the involvement of cardiac resident macrophages in compensatory cardiac growth during hypertension.
- To determine the specific molecular mechanisms by which RMs contribute to cardiac adaptation.
Main Methods:
- Single-cell transcriptomics was employed on fate-mapped cardiac resident macrophages in normotensive and hypertensive animal models.
- Inducible ablation of RMs and genetic deletion of RM-derived insulin-like growth factor-1 (Igf1) were performed.
- Macrophage subpopulations in human cardiomyopathy were analyzed using single-cell transcriptomics.
Main Results:
- Cardiac RMs exhibit diverse transcriptional states, including reparative programs with high Igf1 expression.
- Hypertension induced proliferation and activation of specific RM states, correlating with cardiomyocyte growth.
- Ablation of RMs or deletion of RM-derived Igf1 impaired adaptive cardiomyocyte growth, leading to cardiac dysfunction.
- A conserved IGF1-expressing macrophage subpopulation was identified in human cardiomyopathy.
Conclusions:
- Resident cardiac macrophages are essential for adaptive cardiac growth in response to hypertensive stress.
- Macrophage-derived IGF-1 is a critical mediator of cardiomyocyte hypertrophy and maintenance of cardiac mass.
- These findings highlight a novel cardioprotective role for RMs in hypertension and suggest potential therapeutic targets.
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.
