GSK3[beta] inhibition and canonical Wnt signaling in mice hearts after myocardial ischemic damage

Myocardial infarction induces myocardial injury and tissue damage. During myocardial infarction strong cellular response is initiated to salvage the damaged tissues. This response is associated with the induction of different signaling pathways. Of these, the canonical Wnt signaling is increasingly...

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Veröffentlicht in:PloS one 2019-06, Vol.14 (6), p.e0218098
Hauptverfasser: Badimon, Lina, Casaní, Laura, Camino-Lopez, Sandra, Juan-Babot, Oriol, Borrell-Pages, Maria
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Sprache:eng
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Zusammenfassung:Myocardial infarction induces myocardial injury and tissue damage. During myocardial infarction strong cellular response is initiated to salvage the damaged tissues. This response is associated with the induction of different signaling pathways. Of these, the canonical Wnt signaling is increasingly important for its prosurvival cellular role, making it a good candidate for the search of new molecular targets to develop therapies to prevent heart failure in infarcted patients. Herein we report that GSK3[beta] regulates the canonical Wnt signaling in C57Bl6 mice hearts. GSK3[beta] is a canonical Wnt pathway inhibitor. Using GSK3[beta] inhibitors and inducing myocardial injury (MI) in Lrp5.sup.-/- mice model we show that GSK3[beta] phosphorylation levels regulate downstream canonical Wnt pathway genes in the ischemic heart. In the setting of MI, myocardial damage assessment usually correlates with functional and clinical outcomes. Therefore, we measured myocardial injury size in Wt and Lrp5.sup.-/- mice in the presence and absence of two different GSK3 inhibitors prior to MI. Myocardial injury was independent of GSK3 inhibitor treatments and GSK3[beta] expression levels. These studies support a central role for GSK3[beta] in the activation of the canonical Wnt pathway in the Wt heart. Although LRP5 is protective against myocardial injury, GSK3[beta] expression levels do not regulate heart damage.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0218098