- 作者：Toyoharu Oba ; MD?/sup> ; Hideo Yasukawa ; MD ; PhD?/sup> ; &dagger ; ; yahideo@med.kurume-u.ac.jp ; Masahiko Hoshijima ; MD ; PhD&Dagger ; ; Ken-ichiro Sasaki ; MD ; PhD?/sup> ; &dagger ; ; Nobuyoshi Futamata ; MD?/sup> ; Daisuke Fukui ; MD?/sup> ; Kazutoshi Mawatari ; MD?/sup> ; Takanobu Nagata ; MD?/sup> ; Sachiko Kyogoku ; MD?/sup> ; Hideki Ohshima ; MD?/sup> ; Tomoko Minami ; MD?/sup> ; Keiichiro Nakamura ; MD ; PhD§ ; ; Dongchon Kang ; MD ; PhD?/sup> ; Toshitaka Yajima ; MD ; PhD&Dagger ; ; Kirk U. Knowlton ; MD&Dagger ; ; Tsutomu Imaizumi ; MD ; PhD?/sup> ; &dagger ;
- 关键词：acute myocardial infarction ; cytokine ; JAK-STAT ; left ventricular remodeling ; SOCS3
- 刊名：Journal of the American College of Cardiology
- 出版年：2012
- 出版时间：28 February, 2012
- 年：2012
- 卷：59
- 期：9
- 页码：838-852
- 全文大小：5584 K
Objectives
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.