Exendin-4 improves cardiac function in mice overexpressing monocyte chemoattractant protein-1 in cardiomyocytes

    Authors

    C. W. Younce; J. L. Niu; J. Ayala; M. A. Burmeister; L. H. Smith; P. Kolattukudy;J. E. Ayala

    Comments

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    Abbreviated Journal Title

    J. Mol. Cell. Cardiol.

    Keywords

    Glucagon-like peptide-1; Exendin-4; Monocyte chemoattractant protein-1; Inflammation; Cardiomyopathy; ENDOPLASMIC-RETICULUM STRESS; SIGNALING PATHWAY; ACTIVATION; INHIBITION; BIOLOGY; SERCA2A; AGONIST; HEART; Cardiac & Cardiovascular Systems; Cell Biology

    Abstract

    The incretin hormone glucagon-like peptide-1 (Glp1) is cardioprotective in models of ischemia-reperfusion injury, myocardial infarction and gluco/lipotoxicity. Inflammation is a factor in these models, yet it is unknown whether Glp1 receptor (Glp1r) agonists are protective against cardiac inflammation. We tested the hypothesis that the Glp1r agonist Exendin-4 (Ex4) is cardioprotective in mice with cardiac-specific monocyte chemoattractant protein-1 overexpression. These MHC-MCP1 mice exhibit increased cardiac monocyte infiltration, endoplasmic reticulum (ER) stress, apoptosis, fibrosis and left ventricular dysfunction. Ex4 treatment for 8 weeks improved cardiac function and reduced monocyte infiltration, fibrosis and apoptosis in MHC-MCP1 mice. Ex4 enhanced expression of the ER chaperone glucose-regulated protein-78 (GRP78), decreased expression of the proapoptotic ER stress marker CCAAT/-enhancer-binding protein homologous protein (CHOP) and increased expression of the ER calcium regulator Sarco/Endoplasmic Reticulum Calcium ATPase-2a (SERCA2a). These findings suggest that the Glplr is a viable target for treating cardiomyopathies associated with stimulation of pro-inflammatory factors. CI (c) 2014 Elsevier Ltd. All rights reserved.

    Journal Title

    Journal of Molecular and Cellular Cardiology

    Volume

    76

    Publication Date

    1-1-2015

    Document Type

    Article

    Language

    English

    First Page

    172

    Last Page

    176

    WOS Identifier

    WOS:000344202800021

    ISSN

    0022-2828

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