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CARDIAC REGENERATION

ERBB2–YAP crosstalk mediates cardiac regeneration in mice

Nature Reviews Cardiology volume 18, page 4 (2021)Cite this article

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Crosstalk between the ERBB2 and Hippo–YAP pathways is required for robust cardiac regeneration after myocardial infarction in mice, according to a new study. ERBB2–ERK–YAP mechanotransduction signalling and epithelial–mesenchymal transition (EMT)-like processes in cardiomyocytes (CMs) can trigger cardiac regeneration even after functional deterioration and scarring have been established. “We demonstrate something that has long been thought to be impossible, that heart failure is reversible and that the heart cells themselves, given the right stimulus, hold the key,” remark study investigators Alla Aharonov and Eldad Tzahor.

To use a clinically relevant model of heart failure, the research team assessed the effects of inducing CM-specific transient expression of a constitutively active form of ERBB2 (caERBB2) 3 weeks after mice underwent myocardial infarction. Expression of caERBB2 triggered CM dedifferentiation and proliferation and led to cardiac hypertrophy. Cessation of caERBB2 expression led to CM redifferentiation, hypertrophy reversal, sustained improvement in cardiac function and scar replacement with new CMs, showing that ERBB2 activation must be stopped for regeneration to occur. The ERBB2-mediated regeneration involved EMT, with high expression of EMT-related genes, cytoskeletal remodelling, induction of CM migration capacity and increased extracellular matrix turnover activity.

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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. ERBB2–YAP crosstalk mediates cardiac regeneration in mice. Nat Rev Cardiol 18, 4 (2021). https://doi.org/10.1038/s41569-020-00471-7

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