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PMID: 21324930 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Disease models & mechanisms ·Vol. 4 ·No. 4 ·2011-07-00 ·Pages 469-83

Aisagbonhi O, Rai M, Ryzhov S, Atria N, Feoktistov I, Hatzopoulos AK

Abstract

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.

MeSH Terms
Actins/metabolism Animals Blood Vessels/metabolism,pathology Cells, Cultured Endothelial Cells/metabolism,pathology Endothelium/metabolism,pathology Granulation Tissue/metabolism,pathology Heart Valves/metabolism,pathology Intercellular Signaling Peptides and Proteins/metabolism Mesoderm/metabolism,pathology Mice Models, Biological Myocardial Infarction/metabolism,pathology Myocardium/metabolism,pathology Myofibroblasts/metabolism,pathology Signal Transduction Wnt Proteins/metabolism
Chemicals
Actins Intercellular Signaling Peptides and Proteins Wnt Proteins alpha-smooth muscle actin, mouse
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Aisagbonhi Omonigho
Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University, 2213 Garland Avenue, Nashville, TN 37232-6300, USA.
Rai Meena
Ryzhov Sergey
Atria Nick
Feoktistov Igor
Hatzopoulos Antonis K
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Article Info
Journal
Disease models & mechanisms
Abbr.
Dis Model Mech
ISSN
1754-8411
DOI
10.1242/dmm.006510
Published
2011-07-00
Epub
2011-00-14
Pages
469-83
Language
English
Region
England
NLM ID
101483332
PMCID
PMC3124051
Subset
IM
Grants
NHLBI NIH HHS · R01 HL095787 · United States
NIGMS NIH HHS · T32GM07347 · United States
NHLBI NIH HHS · U01 HL100398 · United States
NHLBI NIH HHS · HL100398 · United States
NIGMS NIH HHS · T32 GM007347 · United States
NHLBI NIH HHS · HL083958 · United States
NHLBI NIH HHS · R01 HL083958 · United States
External Links
PubMed source DOI: 10.1242/dmm.006510 PMC Full Text View journal details
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