Title

Exendin-4 Improves Cardiac Function In Mice Overexpressing Monocyte Chemoattractant Protein-1 In Cardiomyocytes

Keywords

Cardiomyopathy; Exendin-4; Glucagon-like peptide-1; Inflammation; Monocyte chemoattractant protein-1

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 pro-apoptotic 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 Glp1r is a viable target for treating cardiomyopathies associated with stimulation of pro-inflammatory factors.

Publication Date

11-1-2014

Publication Title

Journal of Molecular and Cellular Cardiology

Volume

76

Number of Pages

172-176

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.yjmcc.2014.08.022

Socpus ID

84907735865 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84907735865

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