Abstract
AimsMyocardial 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.MethodsHerein 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.ResultsThese 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.
Highlights
Acute myocardial infarction leads to acute cardiac ischemic injury
Using glycogen synthase kinase 3β (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
These studies support a central role for GSK3β in the activation of the canonical Wnt pathway in the wild type C57BL/6 mice (Wt) heart
Summary
Acute myocardial infarction leads to acute cardiac ischemic injury. Cardiomyocytes in the cardiac tissue downstream from the blocked vessels can be killed within minutes causing a massive and immediate inflammatory response that will clear the injured tissue. This response will promote the formation of a sparse cellular tissue that will be filled in by different cellular processes that include infiltration of myofibroblasts, which will deposit collagen and other extracellular matrix proteins, and activation and proliferation of endothelial cells [2]. A week after the initial ischemic assault a scar will form in the cardiac tissue. A better understanding of the cellular and molecular mechanisms involved in cardiac repair could help design strategies to delay the onset of heart failure in infarcted patients
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