title: MicroRNA-145 repairs infarcted myocardium by accelerating cardiomyocyte autophagy.
abstract: We investigated whether microRNA-145 (miR-145) has a cardioprotective effect in a rabbit model of myocardial infarction (MI) and in H9c2 rat cardiomyoblasts. Rabbits underwent 30 min of coronary occlusion, followed by 2 days or 2 wk of reperfusion. Control microRNA (control group; 2.5 nmol/kg, n = 10) or miR-145 (miR-145 group, 2.5 nmol/kg, n = 10) encapsulated in liposomes was intravenously administered immediately after the start of reperfusion. H9c2 rat cardiomyoblasts were transfected with miR-145. The MI size was significantly smaller in the miR-145 group than in the control group at 2 days and 2 wk post-MI. miR-145 had improved the cardiac function and remodeling at 2 wk post-MI. These effects were reversed by chloroquine. Western blot analysis showed that miR-145 accelerated the transition of LC3B I to II and downregulated p62/SQSTM1 at 2 days or 2 wk after MI, but not at 4 wk, and activated Akt in the ischemic area at 2 days after MI. miR-145 inhibited the growth of H9c2 cells, accelerated the transition of LC3B I to II, and increased phosphorylated Akt in the H9c2 cells at 2 days after miR-145 transfection. Antagomir-145 significantly abolished the morphological change, the transition of LC3B I to II, and the increased phosphorylated Akt induced by miR-145 in H9c2 cells. We determined fibroblast growth factor receptor substrate 2 mRNA to be a target of miR-145, both in an in vivo model and in H9c2 cells. In conclusion, post-MI treatment with miR-145 protected the heart through the induction of cardiomyocyte autophagy by targeting fibroblast growth factor receptor substrate 2.
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan; and.
authors.forename: Kenshi
authors.initials: K
authors.lastname: Higashi
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan; and.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan; and minatos@gifu-u.ac.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Minatoguchi
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan; and.
authors.forename: Shinya
authors.initials: S
authors.lastname: Baba
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan; and.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Iwasa
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan; and.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kanamori
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan; and.
authors.forename: Masanori
authors.initials: M
authors.lastname: Kawasaki
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan; and.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishigaki
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan; and.
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University Gifu, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Kumazaki
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University Gifu, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akao
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan; and.
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D002460:Cell Line; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; C526109:Anxa3 protein, rat; C542511:MIRN145 microRNA, rat; C552089:fibroblast receptor substrate 2, rat
keywords: autophagy; cardiomyocyte; miR-145; myocardial infarction