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Title: The Local Microenvironment Limits The Regenerative Potential Of The Mouse Neonatal Heart
Author: Notari, Mario
Ventura-Rubio, Antoni
Bedford-Guaus, Sylvia J.
Jorba, Ignasi
Mulero, Lola
Navajas Navarro, Daniel
Marti, Mercè
Raya Chamorro, Ángel
Keywords: Malalties cardiovasculars
Ratolins (Animals de laboratori)
Cardiovascular diseases
Mice (Laboratory animals)
Issue Date: 1-May-2018
Publisher: Amer Assoc Advancement Science
Abstract: Neonatal mice have been shown to regenerate their hearts during a transient window of time of approximately 1 week after birth. However, experimental evidence for this phenomenon is not undisputed, because several laboratories have been unable to detect neonatal heart regeneration. We first confirmed that 1-day-old neonatal mice are indeed able to mount a robust regenerative response after heart amputation. We then found that this regenerative ability sharply declines within 48 hours, with hearts of 2-day-old mice responding to amputation with fibrosis, rather than regeneration. By comparing the global transcriptomes of 1- and 2-day-old mouse hearts, we found that most differentially expressed transcripts encode extracellular matrix components and structural constituents of the cytoskeleton. These results suggest that the stiffness of the local microenvironment, rather than cardiac cell-autonomous mechanisms, crucially determines the ability or inability of the heart to regenerate. Testing this hypothesis by pharmacologically decreasing the stiffness of the extracellular matrix in 3-day-old mice, we found that decreased matrix stiffness rescued the ability of mice to regenerate heart tissue after apical resection. Together, our results identify an unexpectedly restricted time window of regenerative competence in the mouse neonatal heart and open new avenues for promoting cardiac regeneration by local modification of the extracellular matrix stiffness.
Note: Reproducció del document publicat a:
It is part of: Science Advances, 2018-05-01, Vol. 4: eaao5553
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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