title: Arrhythmogenic properties of dismantling cadherin-mediated adhesion in murine hearts.
abstract: OBJECTIVE
  To evaluate the arrhythmogenic effects of dismantling cadherin-mediated adhesion by recombinant mouse aminopeptidase N (rmAPN) in murine hearts.
  
  
  METHODS
  rmAPN was incubated with cultured neonatal rat cardiomyocytes as well as being infused in adult mice. The cell-cell connections were immunolabelled and observed by laser confocal microscopy. Disruption of the N-terminal of N-cadherin (N-cad) was detected by western blot and quantitative immunofluorescence. The risk of inducible ventricular tachyarrhythmia was evaluated in mice by an electrophysiological study.
  
  
  RESULTS
  Disrupted cell-cell contact was observed in cultured neonatal rat cardiomyocytes in response to 30-40 ng/µL rmAPN. Loss of the N-terminal in N-cad and altered distribution of connexin 43 (Cx43) were observed in hearts from rmAPN-infused mice. In addition, a reduction of phosphorylated Cx43 was also detected concomitant with redistribution of Cx43. Electrophysiological studies of rmAPN-infused mice showed prolonged QRS duration and increased inducibility of ventricular tachycardias.
  
  
  CONCLUSIONS
  Disruption of N-cad by rmAPN contributes to gap junction remodeling and may elicit arrhythmogenic effects. The disorder of adherent junctions by proteolytic enzymes may play an important role in arrhythmogenic mechanisms in correlated diseases.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Zhu
authors.forename: Hegui
authors.initials: H
authors.lastname: Wang
authors.forename: Xiwen
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Hou
authors.forename: Kejiang
authors.initials: K
authors.lastname: Cao
authors.forename: Jiangang
authors.initials: J
authors.lastname: Zou
keywords: N-cadherin; adherence junction; gap junction; recombinant mouse aminopeptidase N; ventricular tachyarrhythmia
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