Arrhythmogenic properties of dismantling cadherin-mediated adhesion in murine hearts
Hongjun Zhu
Hegui Wang
Xiwen Zhang
Xiaofeng Hou
Kejiang Cao
Jiangang Zou
摘要：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 phosphorylat-ed 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. Conclusion: 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.
机标关键词：ventricular tachyarrhythmianeonatal ratmiceaminopeptidase NN-cadherinwestern blotquantitativegap junction
分类号：R3(基础医学)
资助基金：Health Department of Jiangsu Province(RC2007041)
论文发表日期：2010-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
英文信息