title: Comparison of expression of connexin in right atrial myocardium in patients with chronic atrial fibrillation versus those in sinus rhythm.
abstract: An abnormal distribution of the gap junction occurs in chronic atrial fibrillation (AF). There are conflicting data regarding changes in connexins (Cxs) in experimental models of AF. We examined whether patients with chronic AF have alterations in atrial Cxs. We analyzed the expression of Cx40 and Cx43 in the right atrial myocardium from 10 patients with mitral valvular disease (MVD) who had AF (MVD/AF), 10 patients with MVD who were in normal sinus rhythm (MVD/NSR), and 10 control patients in NSR (tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained before surgery, and an electrophysiologic examination was performed during the operation. An immunohistochemical study was performed on atrial tissue. The relative expression level of Cx40 protein was significantly lower in MVD/AF patients (6.5 +/- 4.6) than in either MVD/NSR patients (17.7 +/- 8.9, p <0.05) or controls (24.7 +/- 11.1, p <0.01). The relative expression level of Cx40 messenger ribonucleic acid was also significantly lower in MVD/AF patients (0.23 +/- 0.13) than in MVD/NSR patients (0.47 +/- 0.26, p <0.01) or controls (0.47 +/- 0.17, p <0.01). For Cx43 protein and messenger ribonucleic acid, there was no significant difference in relative expression levels among the 3 groups. Interestingly, the level of serine-phosphorylated Cx40 was approximately 52% greater in MVD/AF patients than in controls. In MVD/AF patients, the immunoreactive signal of Cx40 was significantly lower than in controls. There was no significant difference in the connective tissue-volume fraction among the groups. Thus, downregulation of Cx40 and abnormal phosphorylation of Cx40 may result in abnormal cell-to-cell communication and alteration in the electrophysiologic properties of the atrium, leading to the initiation and/or perpetuation of AF.
authors.affiliation: Division of Cardiovascular Medicine, Yamaguchi, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nao
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohkusa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hisamatsu
authors.forename: Noriko
authors.initials: N
authors.lastname: Inoue
authors.forename: Tomo
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Jutaro
authors.initials: J
authors.lastname: Yamada
authors.forename: Akihiko
authors.initials: A
authors.lastname: Shimizu
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshiga
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamagata
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yano
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Hamano
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
mesh_terms: D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D002908:Chronic Disease; D018031:Connexin 43 / Q000032:analysis* / Q000235:genetics*; D017630:Connexins / Q000032:analysis* / Q000235:genetics*; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006325:Heart Atria / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D006349:Heart Valve Diseases / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics*; D000097003:Gap Junction alpha-5 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D012333:RNA, Messenger; D000097003:Gap Junction alpha-5 Protein