Exendin-4 improves cardiac function in mice overexpressing monocyte chemoattractant protein-1 in cardiomyocytes
Abbreviated Journal Title
J. Mol. Cell. Cardiol.
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
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 of Molecular and Cellular Cardiology
"Exendin-4 improves cardiac function in mice overexpressing monocyte chemoattractant protein-1 in cardiomyocytes" (2015). Faculty Bibliography 2010s. 6334.