Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition

Despite available therapies, myocardial infarction (MI) remains a leading cause of death worldwide. Better understanding of the molecular and cellular mechanisms that regulate cardiac repair should help to improve the clinical outcome of MI patients. Using the reporter mouse line TOPGAL, we show tha...

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Main Authors:	Aisagbonhi, Omonigho, Rai, Meena, Ryzhov, Sergey, Atria, Nick, Feoktistov, Igor, Hatzopoulos, Antonis K.
Format:	Online
Language:	English
Published:	The Company of Biologists Limited 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124051/

id	pubmed-3124051
recordtype	oai_dc
spelling	pubmed-31240512011-07-02 Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition Aisagbonhi, Omonigho Rai, Meena Ryzhov, Sergey Atria, Nick Feoktistov, Igor Hatzopoulos, Antonis K. Research Article Despite available therapies, myocardial infarction (MI) remains a leading cause of death worldwide. Better understanding of the molecular and cellular mechanisms that regulate cardiac repair should help to improve the clinical outcome of MI patients. Using the reporter mouse line TOPGAL, we show that canonical (β-catenin-dependent) Wnt signaling is induced 4 days after experimental MI in subepicardial endothelial cells and perivascular smooth muscle actin (SMA)-positive (SMA+) cells. At 1 week after ischemic injury, a large number of canonical-Wnt-positive cells accumulated in the infarct area during granulation tissue formation. Coincidently with canonical Wnt activation, endothelial-to-mesenchymal transition (EndMT) was also triggered after MI. Using cell lineage tracing, we show that a significant portion of the canonical-Wnt-marked SMA+ mesenchymal cells is derived from endothelial cells. Canonical Wnt signaling induces mesenchymal characteristics in cultured endothelial cells, suggesting a direct role in EndMT. In conclusion, our study demonstrates that canonical Wnt activation and EndMT are molecular and cellular responses to MI and that canonical Wnt signaling activity is a characteristic property of EndMT-derived mesenchymal cells that take part in cardiac tissue repair after MI. These findings could lead to new strategies to improve the course of cardiac repair by temporal and cell-type-specific manipulation of canonical Wnt signaling. The Company of Biologists Limited 2011-07 2011-02-14 /pmc/articles/PMC3124051/ /pubmed/21324930 http://dx.doi.org/10.1242/dmm.006510 Text en © 2011. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Aisagbonhi, Omonigho Rai, Meena Ryzhov, Sergey Atria, Nick Feoktistov, Igor Hatzopoulos, Antonis K.
spellingShingle	Aisagbonhi, Omonigho Rai, Meena Ryzhov, Sergey Atria, Nick Feoktistov, Igor Hatzopoulos, Antonis K. Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition
author_facet	Aisagbonhi, Omonigho Rai, Meena Ryzhov, Sergey Atria, Nick Feoktistov, Igor Hatzopoulos, Antonis K.
author_sort	Aisagbonhi, Omonigho
title	Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition
title_short	Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition
title_full	Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition
title_fullStr	Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition
title_full_unstemmed	Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition
title_sort	experimental myocardial infarction triggers canonical wnt signaling and endothelial-to-mesenchymal transition
description	Despite available therapies, myocardial infarction (MI) remains a leading cause of death worldwide. Better understanding of the molecular and cellular mechanisms that regulate cardiac repair should help to improve the clinical outcome of MI patients. Using the reporter mouse line TOPGAL, we show that canonical (β-catenin-dependent) Wnt signaling is induced 4 days after experimental MI in subepicardial endothelial cells and perivascular smooth muscle actin (SMA)-positive (SMA+) cells. At 1 week after ischemic injury, a large number of canonical-Wnt-positive cells accumulated in the infarct area during granulation tissue formation. Coincidently with canonical Wnt activation, endothelial-to-mesenchymal transition (EndMT) was also triggered after MI. Using cell lineage tracing, we show that a significant portion of the canonical-Wnt-marked SMA+ mesenchymal cells is derived from endothelial cells. Canonical Wnt signaling induces mesenchymal characteristics in cultured endothelial cells, suggesting a direct role in EndMT. In conclusion, our study demonstrates that canonical Wnt activation and EndMT are molecular and cellular responses to MI and that canonical Wnt signaling activity is a characteristic property of EndMT-derived mesenchymal cells that take part in cardiac tissue repair after MI. These findings could lead to new strategies to improve the course of cardiac repair by temporal and cell-type-specific manipulation of canonical Wnt signaling.
publisher	The Company of Biologists Limited
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124051/
_version_	1611462329923272704

Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition

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