Abstract
Myocardial infarction (MI) is caused by the formation of plaques in the arterial walls, leading to a decrease of blood flow to the heart and myocardium injury as a result of hypoxia. Ferroptosis is a crucial event in myocardial injury, and icariin (ICA) exerts protective effects against myocardial injury. Here, we investigated the protective mechanism of ICA in hypoxia/reoxygenation (H/R)‐induced ferroptosis of cardiomyocytes. H9C2 cells were subjected to H/R induction. The content of lactate dehydrogenase and the levels of oxidative stress and intracellular ferrous ion Fe2+ were measured. The levels of ferroptosis markers (ACSL4 and GPX4) were detected. H/R‐induced H9C2 cells were cultured with ICA in the presence or absence of ferroptosis inducer (erastin). Znpp (an HO‐1 inhibitor) was added to ICA‐treated H/R cells to verify the role of the Nrf2/HO‐1 pathway. H/R‐induced H9C2 cells showed reduced viability, enhanced oxidative stress and lactate dehydrogenase content, increased levels of Fe2+ and ACSL4, and decreased levels of GPX4. ICA inhibited H/R‐induced ferroptosis and oxidative stress in cardiomyocytes. Erastin treatment reversed the inhibitory effect of ICA on ferroptosis in H/R cells. The expression of Nrf2 and HO‐1 in H/R‐induced H9C2 cells was reduced, whereas ICA treatment reversed this trend. Inhibition of the Nrf2/HO‐1 pathway reversed the protective effect of ICA on H/R‐induced ferroptosis. Collectively, our results suggest that ICA attenuates H/R‐induced ferroptosis of cardiomyocytes by activating the Nrf2/HO‐1 signaling pathway.
Highlights
Myocardial infarction (MI) is caused by the formation of plaques in the arterial walls, leading to a decrease of blood flow to the heart and myocardium injury as a result of hypoxia
H9C2 cells were subjected to hypoxia/ reoxygenation (H/R) induction
The results demonstrated that the fluorescence level of reactive oxygen species (ROS) in cells was significantly increased (P < 0.01; Fig. 1E), levels of MDA were increased, and the activities of SOD and CAT were decreased after H/R treatment (P < 0.01; Fig. 1F–H)
Summary
Myocardial infarction (MI) is caused by the formation of plaques in the arterial walls, leading to a decrease of blood flow to the heart and myocardium injury as a result of hypoxia. H/R-induced H9C2 cells showed reduced viability, enhanced oxidative stress and lactate dehydrogenase content, increased levels of Fe2+ and ACSL4, and decreased levels of GPX4. Inhibition of the Nrf2/HO-1 pathway reversed the protective effect of ICA on H/R-induced ferroptosis. Our results suggest that ICA attenuates H/R-induced ferroptosis of cardiomyocytes by activating the Nrf2/HO-1 signaling pathway. Myocardial infarction (MI) is a cardiac event caused by the formation of plaques in the arterial walls leading to the decrease of blood flow to the heart and injury of the myocardium as a result of hypoxia [1]. Targeting the cardiomyocyte death concerning MI/R injury is accepted as a prospective therapeutic strategy
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