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MACROPHAGES

Cardiac macrophages team up to maintain heart health

Nature Reviews Cardiology volume 17, page 757 (2020)Cite this article

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A network of macrophages in the heart supports cardiac health and function by removing dysfunctional mitochondria and waste material from cardiomyocytes, according to a study published in Cell. Cardiomyocytes are under continuous intense mechanical stress and metabolic demand. Given that cardiomyocytes are long-lived and their renewal is extremely low, how myocardial homeostasis is maintained was unclear. Andrés Hidalgo and colleagues now demonstrate that cardiomyocytes in the mouse heart release damaged cellular components, such as defective mitochondria, in subcellular particles called exophers, which are then taken up and eliminated by cardiac macrophages to preserve cardiac stability and function. “These findings set a new paradigm for how tissues maintain long-term quality and is different from the perception that all cells deal with their own waste through autophagy,” highlights Hidalgo. “In the context of immunity, this study provides another striking example of how macrophages tailor their function to the needs of a tissue,” he adds.

Next, the researchers demonstrated that cardiac macrophages actively take up material from surrounding cardiomyocytes in steady state conditions in mice. Hidalgo and colleagues found that a large fraction of waste material, including damaged mitochondria, is ejected from healthy cardiomyocytes in dedicated membranous particles that were analogous to neural exophers described in Caenorhabditis elegans. The cardiomyocyte-derived mitochondria released within the exophers were then taken up by adjacent cardiac macrophages and targeted for degradation. Failure to eliminate the exophers, as occurred in macrophage-depleted mice, resulted in inflammasome activation and autophagy arrest. Notably, the exopher-mediated mitochondrial transfer was increased during cardiac stress conditions.

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  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Irene Fernández-Ruiz

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  1. Irene Fernández-Ruiz
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Correspondence to Irene Fernández-Ruiz.

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Fernández-Ruiz, I. Cardiac macrophages team up to maintain heart health. Nat Rev Cardiol 17, 757 (2020). https://doi.org/10.1038/s41569-020-00461-9

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