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Liraglutide repairs the infarcted heart: The role of the SIRT1/Parkin/mitophagy pathway.
Molecular Medicine Reports 2018 March
Liraglutide is glucagon‑like peptide‑1 receptor agonist used for treating patients with type 2 diabetes mellitus. The present study aimed to investigate the role and mechanism of liraglutide in repairing the infarcted heart following myocardial infarction. The results of the present study demonstrated that amplification of the dose of liraglutide for ~28 days was able to reduce cardiac fibrosis, inflammatory responses and myocardial death in the post‑infarcted heart. In vitro, liraglutide protected cardiomyocyte mitochondria against the chronic hypoxic damage, inhibiting the mitochondrial apoptosis pathways. Mechanistically, liraglutide elevated the expression of NAD‑dependent protein deacetylase sirtuin‑1 (SIRT1), which increased the expression of Parkin, leading to mitophagy activation. Protective mitophagy reversed cellular adenosine 5'‑triphosphate production, reduced cellular oxidative stress and balanced the redox response, sustaining mitochondrial homeostasis. Notably, following blockade of glucagon‑like peptide 1 receptor or knockdown of Parkin, the beneficial effects of liraglutide on mitochondria disappeared. In conclusion, the results of the present study illustrated the protective role of liraglutide in repairing the infarcted heart via regulation of the SIRT1/Parkin/mitophagy pathway.
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