The Human Heart Contains Distinct Macrophage Subsets with Divergent Origins and Functions
By G. Bajpai, Caralin Schneider, Nicole Rose Wong, Andrea L. Bredemeyer, M. Hulsmans, Matthias Nahrendorf, S. Epelman, D. Kreisel, Yongjian Liu, A. Itoh and 4 more. Nature Medicine, 2018
606 citations recorded by the source corpus.
Paradigm-shifting studies in the mouse have identified tissue macrophage heterogeneity as a critical determinant of immune responses. In contrast, surprisingly little is known regarding macrophage heterogeneity in humans. Macrophages within the mouse heart are partitioned into CCR2− and CCR2+ subsets with divergent origins, repopulation mechanisms, and functions. Here, we demonstrate that the human myocardium also contains distinct subsets of CCR2− and CCR2+ macrophages. Analysis of sex-mismatched heart transplant recipients revealed that CCR2− macrophages are a tissue-resident population exclusively replenished through local proliferation, whereas CCR2+ macrophages are maintained through monocyte recruitment and proliferation. Moreover, CCR2− and CCR2+ macrophages have distinct functional properties, analogous to reparative CCR2− and inflammatory CCR2+ macrophages in the mouse heart. Clinically, CCR2+ macrophage abundance is associated with left ventricular remodeling and systolic function in heart failure patients. Collectively, these observations provide initial evidence for the functional importance of macrophage heterogeneity in the human heart. Study of macrophage heterogeneity in human hearts reveals a subset of inflammatory macrophages that is associated with cardiac dysfunction in patients with heart failure.
Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/45322fbba2057a11be7583ab193c016ccc249f4a
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In Molecular Biology
Citations in the corpus
- Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction (2018, positive): “In addition, preventing monocyte influx in adult mice has been demonstrated to have beneficial effects when excessive inflammation drives ischemic injury 33, 34 .”
- Diversity, Mechanisms and Significance of Macrophage Plasticity (2019, background): “In many adult murine tissues, the resident population of mononuclear phagocytes is a mix of cells originating during development and circulating monocytic precursors (2, 14), as illustrated by heart macrophages (15).”