title: Enhanced ADAM17 expression is associated with cardiac remodeling in rats with acute myocardial infarction.
abstract: OBJECTIVE
  This study aimed to investigate the dynamic expression of A-disintegrin-and-metalloproteinase-17 (ADAM17) during cardiac remodeling after acute myocardial infarction (AMI).
  
  
  METHODS
  Forty male Wistar rats with a permanent ligation of the left anterior descending artery were equally divided into four groups based on predefined sacrifice time: MI1d, MI1w, MI4w and MI12w. As controls, 36 rats only with left thoracotomy were equally divided into four groups. Cardiac remodeling was assessed by echocardiography and hematoxylin and eosin (H&E) staining. ADAM17 mRNA was detected by real-time reverse transcription polymerase chain reaction, and protein expression of ADAM17, tissue inhibitor of metalloproteinases-3 (TIMP-3) and TNF-α was analyzed by western blotting.
  
  
  RESULTS
  The systolic function was sharply worsened in the MI1w group (versus the Con1w group, P<0.05), but left ventricular weight index was significantly increased after 4weeks post-MI (P<0.05). H&E staining revealed that one week after AMI, myocardial tissue in the epicardial border zone of the infarcted heart was mixed with broken mitochondrial cristae and decreased matrix density. ADAM17 mRNA and protein expression was significantly increased, accompanied by decreased TIMP-3 and upregulated TNF-α expression in the MI1w group (versus the MI1d group, all P<0.05). Moreover, dynamic ADAM17 mRNA expression was positively correlated with enlarged LVEDd and LVESd (P=0.001, P=0.003) and negatively with LVEF (P=0.039) in AMI rats.
  
  
  CONCLUSIONS
  Enhanced ADAM17 expression, along with decreased TIMP-3 and increased TNF-α expression, especially within one week after AMI, is associated with cardiac remodeling.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital, Harbin Medical University, Harbin 150086, PR China.
authors.forename: Dong-You
authors.initials: DY
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, PR China. Electronic address: hrbzyz@sina.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Cardiology Ultrasound, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, PR China.
authors.forename: Jie-Mei
authors.initials: JM
authors.lastname: Yang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, PR China.
authors.forename: Xing-Tong
authors.initials: XT
authors.lastname: Zhang
mesh_terms: D000072198:ADAM17 Protein / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002097:C-Reactive Protein / Q000096:biosynthesis; D004452:Echocardiography; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000473:pathology; D008297:Male; D008929:Mitochondria, Heart / Q000473:pathology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: D019717:Tissue Inhibitor of Metalloproteinase-3; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat
keywords: A disintegrin and metalloproteinase-17; Left ventricle; Myocardial infarction; Myocardial remodeling; Tissue inhibitor of metalloproteinase-3; Tumor necrosis factor-α