GSK3 beta inhibition and canonical Wnt signaling in mice hearts after myocardial ischemic damage
Por:
Badimon, L, Casani, L, Camino-Lopez, S, Juan-Babot, O, Borrell-Pages, M
Publicada:
20 jun 2019
Resumen:
Aims
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.
Methods
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(-/-) 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(-/-) 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.
Results
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.
Filiaciones:
Badimon, L:
Hosp Santa Creu & Sant Pau, Inst Recerca, Cardiovasc Program ICCC, Barcelona, Spain
Inst Salud Carlos III, CIBER CV, Madrid, Spain
UAB, Cardiovasc Res Chair, Barcelona, Spain
Casani, L:
Hosp Santa Creu & Sant Pau, Inst Recerca, Cardiovasc Program ICCC, Barcelona, Spain
Camino-Lopez, S:
Hosp Santa Creu & Sant Pau, Inst Recerca, Cardiovasc Program ICCC, Barcelona, Spain
Juan-Babot, O:
Hosp Santa Creu & Sant Pau, Inst Recerca, Cardiovasc Program ICCC, Barcelona, Spain
Borrell-Pages, M:
Hosp Santa Creu & Sant Pau, Inst Recerca, Cardiovasc Program ICCC, Barcelona, Spain
Inst Salud Carlos III, CIBER CV, Madrid, Spain
Gold, Green Published
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