Expression of connexins 40 and 43 in human left atrium in atrial fibrillation of different aetiologies

Abstract

Objective: To test the hypothesis that atrial fibrillation (AF) is associated with changes in the expression of connexins 40 and 43 in the left atrium with more pronounced changes in mitral valve disease than in lone AF. Methods: Protein concentrations of connexin 40 and connexin 43 were analysed in left atrial tissue of patients undergoing cardiac surgery. One group of patients had lone AF (n = 41), one group had AF and mitral valve repair (n = 36), and one group in sinus rhythm served as controls (n = 15). Results: Western blot analysis of connexin 40 and connexin 43 expression showed an increase of both gap junctional proteins (connexin 43 . connexin 40) in patients with AF of all forms compared with patients in sinus rhythm (p = 0.01 and p = 0.011, respectively). Subgroup analysis showed increased concentrations of connexin 40 in lone AF and AF with mitral valve disease compared with sinus rhythm (p = 0.06 and p = 0.029, respectively), whereas the same analysis for connexin 43 reached significance only in the mitral valve disease group (p = 0.031). No differences in connexin 40 and connexin 43 expression were detectable between lone AF and AF with mitral valve disease. Within the groups connexin 40 and connexin 43 expression did not differ between patients with paroxysmal AF and patients with chronic AF.Conclusion: The present study shows for the first time that AF can induce changes in the left atrium with increased connexin expression. Furthermore, no systematic differences between patients with paroxysmal and chronic AF were detected.

Activin Receptor‐Like Kinase 4 Haplodeficiency Mitigates Arrhythmogenic Atrial Remodeling and Vulnerability to Atrial Fibrillation in Cardiac Pathological Hypertrophy

“…The vast majority of studies suggest that reduced abundance of Cx40 and heterogeneity of its distribution were common in atrial tissues from patients with AF 38, 39, 40. There have been many conflicting results regarding the precise changes of Cx43 in AF 39, 41. At the animal level, transverse aortic constriction induced an increase in tyrosine phosphorylation of Cx43 in mice,42 and downregulation of Cx43 expression was observed in LA and LV tissues of pressure‐overloaded heart compared with that in the corresponding sham models 37, 42.…”

Is there a role for remodeled connexins in AF? No simple answers

“…In the goat model of AF the appearance of increased heterogeneity without a change in Cx40 quantity paralleled the progression from unsustained to sustained AF [86]. An increase in Cx43 has also been measured [82,87,88], as well as a decrease [49] but the most common finding is no change [47,54,84,85]. Unlike Cx40, Cx43 is uniformly distributed rather than inhomogeneously distributed but like Cx40, lateralization of Cx43 has been observed [49,84].…”

“…Connexin quantification in left atrium has rarely been done [82,83]. Increased Cx40 [47,49,82,84], decreased Cx40 [49,54,85] and no change in Cx40 [54,83] have been reported.…”

“…Connexin quantification in left atrium has rarely been done [82,83]. Increased Cx40 [47,49,82,84], decreased Cx40 [49,54,85] and no change in Cx40 [54,83] have been reported. A common finding irrespective of quantitative changes in humans or animal models has been an increased heterogeneity in Cx40 distribution manifested as increased regions in which Cx40 containing myocytes are located adjacent to myocytes mostly lacking Cx40 [47,49,54,83,85,86].…”

Atrial Remodeling And Atrial Fibrillation: Mechanistic Interactions And Clinical Implications

“…23 Whether AF-induced changes in these connexins play a significant role in atrial remodeling remains a subject of debate. 23 AF has been shown to be associated with a net increase 24,25 or decrease 26,27 in connexin 40 expression with redistribution to the lateral borders of the atrial myocytes.This may result in anisotropy and dispersion of atrial conduction, thus favoring an environment vulnerable to AF.…”