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Exendin4 inhibits atrial arrhythmogenesis in a model of myocardial infarctioninduced heart failure via the GLP1 receptor signaling pathway

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Glucagonlike peptide1 receptor (GLP1 receptor) agonists are considered to exert cardioprotective effects in models of acute and chronic heart disease. The present study aimed to investigate the role of exendin4 (a GLP1 receptor agonist) in atrial arrhythmogenesis in a model of myocardial infarction (MI)induced heart failure and to elucidate the mechanisms underlying its effects. For this purpose, male SpragueDawley rats underwent sham surgery or left anterior descending artery ligation prior to being treated with saline/exendin4/exendin4 plus exendin939 (an antagonist of GLP1 receptor) for 4¬†weeks. The effects of exendin4 on atrial electrophysiology, atrial fibrosis and PI3K/AKT signaling were assessed. Rats with MI exhibited depressed left ventricular function, an enlarged left atrium volume, prolonged action potential duration, elevated atrial tachyarrhythmia inducibility, decreased conduction velocity and an increased total activation time, as well as total activation time dispersion and atrial fibrosis. However, these abnormalities were attenuated by treatment with the GLP1 receptor agonist, exendin4. Moreover, the expression levels of collagen I, collagen III, transforming growth factorβ1, phosphorylated PI3K and AKT levels in atrial tissues were upregulated in rats with MI. These changes were also attenuated by exendin4. It was also found that these exedin4mediated attenutations were mitigated by the coadministration of exendin939 with exendin4. Overall, the findings of the present study suggested that exendin4 decreases susceptibility to atrial arrhythmogenesis, improves conduction properties and exerts antifibrotic effects via the GLP1 receptor signaling pathway. These findings provide evidence for the potential use of GLP1R in the treatment of atrial fibrillation.
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Document Type: Research Article

Affiliations: 1: Department of Cardiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China 2: Department of Orthopedic Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China 3: Department of Cardiology, Qian Xi Nan People's Hospital, Bijie, Guizhou 562400, P.R. China

Publication date: October 1, 2020

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  • Experimental and Therapeutic Medicine aims to ensure the expedient publication, in both print and electronic format, of studies relating to biology, gene therapy, infectious disease, microbiology, molecular cardiology and molecular surgery. The journal welcomes studies pertaining to all aspects of molecular medicine, and studies relating to in vitro or in vivo experimental model systems relevant to the mechanisms of disease are also included.

    All materials submitted to this journal undergo the appropriate review via referees who are experts in this field. All materials submitted follow international guidelines with regard to approval of experiments on humans and animals.
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