title: Remodelling of myocardial intercalated disc protein connexin 43 causes increased susceptibility to malignant arrhythmias in ARVC/D patients.
abstract: BACKGROUND
  Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a primary cardiomyopathy characterised by fibrofatty replacement and ventricular arrhythmias. The occurrence of malignant arrhythmias may be associated with fatty infiltration and intercalated disk remodelling, but the specific pathological remodelling pattern is not yet clear.
  
  
  METHODS
  Twelve explanted hearts from patients diagnosed with ARVC/D according to the 2010 Task Force Criteria and pathology examination were divided into two groups with (SVT, n=6) or without (non-SVT, n=6) recurrent sustained ventricular tachycardia (SVT) before heart transplantation. Six ARVC autopsy hearts and six normal donor hearts were also collected. We evaluated the fibrofatty infiltration by Masson staining and the expression of intercalated disc proteins through immunohistochemistry staining combined with western blot using the ventricular tissue of ARVC as well as normal hearts.
  
  
  RESULTS
  There was significant fatty replacement in the right ventricles of both the SVT and the non-SVT groups compared to normal hearts, but no significant differences were found in fibre, fatty and residual myocardium components between these two groups. Immunohistochemistry and western blot further showed disturbed distribution and significantly reduced expression of Connexin 43 (Cx43) in the SVT group (SVT vs. Normal P=0.010, SVT vs. non-SVT P=0.012). No significantly diminished expression was found in the non-SVT group. The cardiac histology of ARVC/D patients with sudden death verified by forensic pathology confirmed a similar phenomenon.
  
  
  CONCLUSIONS
  Our pathology study on explanted and autopsied hearts indicates that the expression of Cx43 was significantly reduced and disturbed in distribution in ARVC/D myocardium with sustained ventricular tachycardia, but not in patients without malignant ventricular arrhythmias. This implies a correlation between Cx43 remodelling and malignant arrhythmias in ARVC/D patients.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, PR China.
authors.forename: Zhenglian
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei 430030, PR China. Electronic address: xschen@mail.hust.edu.cn.
authors.forename: Xinshan
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, PR China. Electronic address: fwsongjiangping@126.com.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Song
mesh_terms: D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D016022:Case-Control Studies; D018031:Connexin 43 / Q000378:metabolism*; D016757:Death, Sudden, Cardiac; D004198:Disease Susceptibility; D005260:Female; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D017180:Tachycardia, Ventricular / Q000378:metabolism*
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human
keywords: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D); Connexin 43; Implanted cardiac defibrillators; Sudden cardiac death