GSK3β inhibition and canonical Wnt signaling in mice hearts after myocardial ischemic damage

• Published in: PloS one Vol. 14; no. 6; p. e0218098
• Main Authors: Badimon, Lina, Casaní, Laura, Camino-Lopez, Sandra, Juan-Babot, Oriol, Borrell-Pages, Maria
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.06.2019; Public Library of Science (PLoS)
• Subjects: Animals; Biology and Life Sciences; Cardiac function; Congestive heart failure; Damage assessment; Gene Expression; Glycogen Synthase Kinase 3 beta - antagonists & inhibitors; Heart attacks; Heart failure; Inhibitors; Injuries; Ischemia; Kinases; Ligands; Low Density Lipoprotein Receptor-Related Protein-5 - genetics; LRP5 protein; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial infarction; Myocardial Ischemia - drug therapy; Myocardial Ischemia - enzymology; Myocardial Ischemia - metabolism; Myocardial Ischemia - pathology; Myocardium - enzymology; Myocardium - metabolism; Permeability; Phosphorylation; Protein Kinase Inhibitors - pharmacology; Proteins; Pyridines - therapeutic use; Pyrimidines - therapeutic use; Research and Analysis Methods; Rodents; Salvage; Signal transduction; Signaling; Vascular endothelial growth factor; Wnt protein; Wnt Signaling Pathway - genetics; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0218098

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 GSK3β regulates the canonical Wnt signaling in C57Bl6 mice hearts. GSK3β is a canonical Wnt pathway inhibitor. Using GSK3β inhibitors and inducing myocardial injury (MI) in Lrp5-/- mice model we show that GSK3β 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-/- mice in the presence and absence of two different GSK3 inhibitors prior to MI. Myocardial injury was independent of GSK3 inhibitor treatments and GSK3β expression levels. These studies support a central role for GSK3β in the activation of the canonical Wnt pathway in the Wt heart. Although LRP5 is protective against myocardial injury, GSK3β expression levels do not regulate heart damage.