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. 2021 Jan 12;8:621644. doi: 10.3389/fcell.2020.621644

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Copyright © 2021 Silva, Pereira, Fonseca, Pinto-do-Ó and Nascimento.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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ECM composition during regenerative (fetal/neonate) and reparative (adult) stages. The composition of the ECM changes around birth, resulting in a stiffer and less regenerative environment. In the fetal–neonatal heart, agrin and periostin stimulate cardiomyocyte proliferation and neovascularization, thus promoting regeneration of the tissue. During adult heart repair, increased expression of fetal-associated ECM is observed, namely, through the expression of FN and hyaluronan. However, this reactivation of the fetal program is incomplete, and adult cardiomyocytes are unable to proliferate, resulting in the formation of a collagen-rich scar.