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- Hu Jianqiang and
- Dongdong Sun
Myocardial infarction (MI), which is characterized by chamber dilation and left ventricular (LV) dysfunction, is associated with substantially higher mortality. We investigated the effects and underlying mechanisms of Luteolin on postinfarction cardiac dysfunction.
MI was constructed by left anterior descending (LAD) coronary artery ligation. In vitro, cultured neonatal cardiomyocytes subjected to simulated MI were used to probe mechanism.
Luteolin significantly improved cardiac function, decreased cardiac enzyme and inflammatory cytokines release after MI. Enhanced autophagic flux as indicated by more GFP-LC3 puncta, less accumulation of aggresomes and P62 in the neonatal cardiomyocytes after hypoxia was observed in the Luteolin pretreatment group. Western blot analysis also demonstrated that Luteolin up-regulated autophagy in the cardiomyocytes subjected to simulated MI injury. Furthermore, Luteolin increased mitochondrial membrane potential, ATP content, citrate synthase (CS) activity and complexesI/II/III/IV/Vactivities in the cardiomyocytes subjected to simulated MI injury. Interestingly, Mst1 (mammalian Ste20-like kinase 1) knockout abolished the protective effects of Luteolin administration.
Luteolin enhances cardiac function, reduces cardiac enzyme and inflammatory markers release after MI. The protective effects of Luteolin are associated with up-regulation of autophagy and improvement of mitochondrial biogenesis through Mst1 inhibition.