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Early life stress regulates cardiac development through an IL4-glucocorticoid signaling balance

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Item Type:Article
Title:Early life stress regulates cardiac development through an IL4-glucocorticoid signaling balance
Creators Name:Apaydin, D.C. and Jaramillo, P.A.M. and Corradi, L. and Cosco, F. and Rathjen, F.G. and Kammertoens, T. and Filosa, A. and Sawamiphak, S.
Abstract:Stressful experiences early in life can increase the risk of cardiovascular diseases. However, it remains largely unknown how stress influences susceptibility to the disease onset. Here, we show that exposure to brain-processed stress disrupts myocardial growth by reducing cardiomyocyte mitotic activity. Activation of the glucocorticoid receptor (GR), the primary stress response pathway, reduces cardiomyocyte numbers, disrupts trabecular formation, and leads to contractile dysfunction of the developing myocardium. However, a physiological level of GR signaling is required to prevent cardiomyocyte hyperproliferation. Mechanistically, we identify an antagonistic interaction between the GR and the cytokine interleukin-4 (IL-4) as a key player in cardiac development. IL-4 signals transcription of key regulators of cell-cycle progression in cardiomyocytes via signal transducer and activator of transcription 3 (Stat3). GR, on the contrary, inhibits this signaling system. Thus, our findings uncover an interplay between stress and immune signaling pathways critical to orchestrating physiological growth of the heart.
Keywords:Stress, Cytokine, Interleukin-4, Glucocorticoid, Heart Development, Cardiomyocyte, Stat3, Animals, Zebrafish, Mice
Source:Cell Reports
Publisher:Cell Press / Elsevier
Page Range:108404
Date:17 November 2020
Official Publication:https://doi.org/10.1016/j.celrep.2020.108404
PubMed:View item in PubMed

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