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Discriminating between myocytes vs. fibroblasts mechanosensation in heart scarring: news from lower vertebrates

Yap is Required for Scar Formation but not Myocyte Proliferation During Heart Regeneration in Zebrafish Commented by Maurizio Pesce

Basic Science - Cardiac Diseases - Fibrosis


A role for YAP mechanotransduction-activated transcription factor in cardiac cell proliferation and control of heart size has been previously described in mammalians (1), where it further promotes cardiac regeneration in neonatal hearts (2). Paradoxically, an activation of the YAP-dependent pathway was observed in cardiac mesenchymal cells in response to cytoskeleton tensioning and myocardial damage in adults (3), suggesting a role in myocardial remodeling.

By taking advantage of the zebrafish system, a known model of cardiac regeneration, Flinn and Colleagues demonstrate that YAP knockdown reduces scar formation in the adult zebrafish heart, but does not interfere with post-injury myocyte mitotic reactivation.

By siRNA-mediated knockdown in rat cardiac fibroblasts, they show that YAP controls specifically genes related to collagen synthesis, again suggesting a role in fibrosis and scar formation in adults.

Taken together, these results establish a link between cardiac growth and scarring mediated by mechanotransduction dependent pathways. In particular, tt will be interesting to understand whether selective knocking down YAP in fibroblasts in the adult mammalian heart, has any impact on heart regeneration.

References


(1) Sci Signal. 2011 Oct 25;4(196):ra70. doi: 10.1126/scisignal.2002278.

(2) Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):13839-44. doi: 10.1073/pnas.1313192110

(3) ACS Nano. 2014 Mar 25;8(3):2033-47. doi: 10.1021/nn4058984.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.