Liraglutide repairs the infarcted heart: The role of the SIRT1/Parkin/mitophagy pathway

Abstract

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.

CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis

“…Mitophagy is a selective autophagy process that regulates cellular metabolism by specifically degrading damaged or redundant mitochondria in the cells [41][42][43] . Mitophagy has been associated with the progression of several diseases [44][45][46][47] . PINK1/ Parkin mitophagy pathway has been identified as a classical pathway involved in mitophagy 48 .…”

Mitophagy in Cardiovascular Diseases

“…This upregulation can be counteracted by multiple types of treatments, such as those involving the use of the superoxide dismutase (SOD) mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL) and mitoTEMPOL [176,177], which counteract age-related mitophagy impairment associated with diseases. Other modulators of mitophagy mediators are zinc [178] and liraglutide [179]. Zinc is able to ensure proper mitophagic pathway signaling through PINK1 and Beclin1 by limiting ROS generation and mitochondrial membrane potential dissipation, while liraglutide, an agonist of the glucagon-like peptide 1 (GLP1) receptor, upregulates the sirtuin 1 (SIRT1) pathway, promoting Parkin-mediated mitophagy, and has already been validated as a molecule useful for the repair of infarcted hearts.…”

Mitochondrial quality control in cardiac cells: Mechanisms and role in cardiac cell injury and disease

“…However, mice with Parkin‐deficient in their hearts showed decreased cardiac function and larger infarct size compared with control mice after MI (Kubli et al, ). Parkin‐mediated mitophagy maintained mitochondrial homeostasis and thereby prevented heart failure progression in mice with a transverse aortic constriction (B. Wang et al, ) and in rats with injured hearts after MI (Qiao et al, ).…”