Zonula occludens-1 and connexin 43 expression in the failing human heart.
Focal disorganization of gap junctional distribution and down-regulation of the major gap junctional protein connexin 43 are typical features of myocardial remodelling in the failing human heart. Increasing evidence indicates that connexin 43 interacts with zonula-occludens-1 (ZO-1), and it has recently been shown that ZO-1 promotes the formation and growth of gap junctional plaques. In the present study, distribution patterns of ZO-1 and connexin 43 were studied in normal and in heart failure patients using double-label immunohistochemistry and confocal microscopy. ZO-1 was found to be co-localized with connexin 43 at intercalated disks. Importantly, in patients with heart failure due to dilated or ischaemic cardiomyopathy, areas of diminished connexin 43 expression were characterized by a markedly reduced ZO-1 staining. Based on these data it is concluded that in patients with heart failure, down-regulation of ZO-1 matches the diminished expression levels of connexin 43, suggesting that ZO-1 plays an important role in gap junction formation and gap junction plaque stability.
Kostin
Sawa
S
Core Lab for Molecular and Structural Biology, W. G. Kerckhoff Institute, Max-Planck Institute for Heart and Lung Research, Parkstrasse 1, 61231 Bad Nauheim, Germany. sawa.kostin@mpi-bn.mpg.de
D018031:Connexin 43 / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019108:Tight Junctions / Q000378:metabolism*
D018031:Connexin 43