Embryonic Stem Cells: A Biological Tool to Translate the Mechanisms of Heart Development

Aisagbonhi, Omonigho; Hatzopoulos, Antonis K.

doi:10.1007/978-3-642-11865-4_23

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“…It is also possible that gain- and loss-of-function approaches differentially trigger competing molecules such as the retinoic acid receptor, which has been shown to prevent stabilized β-catenin from interacting with TCF/LEF factors and activating transcription of target genes ( Easwaran et al, 1999 ). Finally, the cell specificity and timing of canonical Wnt pathway activation or suppression probably play a cell-type- and phase-dependent role in the MI response, comparable to the described stage-specific roles of the Wnt pathway in heart development ( Aisagbonhi and Hatzopoulos, 2011 ).…”

Section: Introductionmentioning

confidence: 58%

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

Aisagbonhi

Rai

Ryzhov

et al. 2011

Disease Models &Amp; Mechanisms

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SUMMARYDespite 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.

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Section: Introductionmentioning

confidence: 58%