title: Cardiac-specific deletion of SOCS-3 prevents development of left ventricular remodeling after acute myocardial infarction.
abstract: OBJECTIVE
  The study investigated the role of myocardial suppressor of cytokine signaling-3 (SOCS3), an intrinsic negative feedback regulator of the janus kinase and signal transducer and activator of transcription (JAK-STAT) signaling pathway, in the development of left ventricular (LV) remodeling after acute myocardial infarction (AMI).
  
  
  BACKGROUND
  LV remodeling after AMI results in poor cardiac performance leading to heart failure. Although it has been shown that JAK-STAT-activating cytokines prevent LV remodeling after AMI in animals, little is known about the role of SOCS3 in this process.
  
  
  METHODS
  Cardiac-specific SOCS3 knockout mice (SOCS3-CKO) were generated and subjected to AMI induced by permanent ligation of the left anterior descending coronary artery.
  
  
  RESULTS
  Although the initial infarct size after coronary occlusion measured by triphenyltetrazolium chloride staining was comparable between SOCS3-CKO and control mice, the infarct size 14 days after AMI was remarkably inhibited in SOCS3-CKO, indicating that progression of LV remodeling after AMI was prevented in SOCS3-CKO hearts. Prompt and marked up-regulations of multiple JAK-STAT-activating cytokines including leukemia inhibitory factor and granulocyte colony-stimulating factor (G-CSF) were observed within the heart following AMI. Cardiac-specific SOCS3 deletion enhanced multiple cardioprotective signaling pathways including STAT3, AKT, and extracellular signal-regulated kinase (ERK)-1/2, while inhibiting myocardial apoptosis and fibrosis as well as augmenting antioxidant expression.
  
  
  CONCLUSIONS
  Enhanced activation of cardioprotective signaling pathways by inhibiting myocardial SOCS3 expression prevented LV remodeling after AMI. Our data suggest that myocardial SOCS3 may be a key molecule in the development of LV remodeling after AMI.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Japan.
authors.forename: Toyoharu
authors.initials: T
authors.lastname: Oba
authors.forename: Hideo
authors.initials: H
authors.lastname: Yasukawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hoshijima
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Sasaki
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Futamata
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fukui
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Mawatari
authors.forename: Takanobu
authors.initials: T
authors.lastname: Nagata
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kyogoku
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohshima
authors.forename: Tomoko
authors.initials: T
authors.lastname: Minami
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Nakamura
authors.forename: Dongchon
authors.initials: D
authors.lastname: Kang
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Yajima
authors.forename: Kirk U
authors.initials: KU
authors.lastname: Knowlton
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Imaizumi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D018450:Disease Progression; D004452:Echocardiography; D017353:Gene Deletion; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000235:genetics*; D015854:Up-Regulation; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D012313:RNA