Abstract
This study was conducted to estimate the protective effect of Cyanidin-3-glucoside (C3G) on myocardial ischemia-reperfusion (IR) injury and to explore its mechanism. The rats were subjected to left anterior descending ligation and perfusion surgery. In vitro experiments were performed on H9c2 cells using the oxygen-glucose deprivation/reoxygenation (OGD/R) model. The results showed the administration of C3G reduced the infarction area, mitigated pathological alterations, inhibited ST segment elevation, and attenuated oxidative stress and ferroptosis-related protein expression. C3G also suppressed the expressions of USP19, Beclin1, NCOA4, and LC3II/LC3I. In addition, treatment with C3G relieved oxidative stress, downregulated LC3II/LC3I, reduced autophagosome number, downregulated TfR1 expression, and upregulated the expressions of FTH1 and GPX4 in OGD/R-induced H9c2 cells. C3G could inhibit the protein levels of USP19 and LC3II. C3G promoted K11-linked ubiquitination of Beclin1. Further evidence that C3G reduced ferroptosis and ameliorated myocardial I/R injury was demonstrated with the ferroptosis promoter RSL3. Taken together, C3G could be a potential agent to protect myocardium from myocardial I/R injury.
Highlights
Cardiovascular disease is a major health problem in industrialised and developing countries, and the high morbidity and mortality have brought heavy healthy and economic burden on society
The above results demonstrated that myocardial ischemiareperfusion causes structural and functional injury to the heart and that C3G treatment could ameliorate the myocardial I/R injury
Our results suggested that the protective effect of C3G on oxygen-glucose deprivation/reoxygenation (OGD/R)-exposed H9c2 cells might be related to the inhibition of autophagy
Summary
Cardiovascular disease is a major health problem in industrialised and developing countries, and the high morbidity and mortality have brought heavy healthy and economic burden on society. Cardiac ischemia causes heart tissue damage and myocardial cell necrosis. Pharmacological treatments and early reperfusion therapies can ameliorate the damage; these therapies can cause irreversible myocardial ischemia/reperfusion (I/R) injury, such as deterioration of cardiac function and arrhythmia [1]. Ferroptosis is a programmed cell death mediator dependent on iron and ROS [2]. As a programmed cell death, ferroptosis induces various lipid hydroperoxiderelated diseases, including myocardial I/R lesions [3]. In myocardial I/R injury, mild autophagy can maintain the intracellular environment and improve the cell survival, but excessive autophagy can cause increased levels of intracellular oxidative stress [4, 5]. The relationship between autophagy and ferroptosis in cardiac ischemiareperfusion has been limited reported
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