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Glycogen‐Synthase Kinase‐3beta/beta‐Catenin Axis Promotes Myocardial Angiogenesis: Role of VEGF
Author(s) -
Thirunavukkarasu Mahesh,
Maulik Nilanjana
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.489.11
Subject(s) - angiogenesis , gsk 3 , gsk3b , microbiology and biotechnology , cardioprotection , catenin , vascular endothelial growth factor , survivin , beta catenin , vascular endothelial growth factor a , chemistry , cancer research , phosphorylation , biology , signal transduction , medicine , wnt signaling pathway , ischemia , apoptosis , vegf receptors , biochemistry
The GSK‐3β/β‐catenin axis is one of most interesting pathways involved in the molecular mechanism of angiogenesis. Recently we have shown the critical role of GSK‐3β/β‐catenin in ischemic preconditioning (IP) mediated angiogenesis. We have observed for the first time that IP induces the β‐catenin driven expression of vascular endothelial growth factor (VEGF), Bcl‐2, survivin in chronic rat myocardial infarction (MI) model increasing the vessel density improving myocardial function. β‐catenin is found to be a critical mediator during angiogenesis & it is phosphorylated by GSK‐3β. During IP induction of the PI‐3 kinase pathway leads to phosphorylation of GSK‐3β, leading to the release, accumulation of β‐catenin in cytosol & the subsequent translocation of β‐catenin into the nucleus drives the expression of its target genes (VEGF, Bcl‐2, survivin) through activation of the T‐cell transcription factors/lymphoid‐ enhancer binding factor transcription factors. These astounding results paved the way for the induction of angiogenesis in the ischemic heart by administration of β‐catenin after an MI which depicted cardioprotection as was observed with IP. The efficacy of β‐catenin overexpression in the induction of collateral vessel formation remodeling was further ascertained by Adeno –shRNA‐β‐catenin to silence the gene expression of β‐catenin thereby abolishing the IP mediated cardioprotection.