title: Luteolin alleviates post-infarction cardiac dysfunction by up-regulating autophagy through Mst1 inhibition.
abstract: Myocardial infarction (MI), which is characterized by chamber dilation and LV dysfunction, is associated with substantially higher mortality. We investigated the effects and underlying mechanisms of Luteolin on post-infarction cardiac dysfunction. Myocardial infarction was constructed by left anterior descending 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 autophagosomes puncta, less accumulation of aggresomes and P62 in the neonatal cardiomyocytes after hypoxia was observed in the Luteolin pre-treatment 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, adenosine triphosphate content, citrate synthase activity and complexes I/II/III/IV/V activities in the cardiomyocytes subjected to simulated MI injury. Interestingly, mammalian sterile 20-like kinase 1 (Mst1) 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.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Wanrong
authors.initials: W
authors.lastname: Man
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Congye
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Rongqing
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Erhe
authors.initials: E
authors.lastname: Gao
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Haichang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D047311:Luteolin / Q000494:pharmacology* / Q000627:therapeutic use; D053078:Membrane Potential, Mitochondrial; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D013318:Stroke Volume; D015854:Up-Regulation; D000099317:Hippo Kinases
chemical_list: D002316:Cardiotonic Agents; D047311:Luteolin; D017346:Protein Serine-Threonine Kinases; C490660:Stk4 protein, mouse; D000099317:Hippo Kinases
keywords: autophagy; luteolin; mammalian Ste20-like kinase 1; myocardial infarction