Claudin-5 Levels Are Reduced in Human End-Stage Cardiomyopathy
Document Type
Article
Publication Date
7-1-2008
Description
Claudin-5 is a transmembrane cell junction protein that is a component of tight junctions in endothelial cell layers. We have previously shown that claudin-5 also localizes to lateral membranes of murine cardiomyocytes at their junction with the extracellular matrix. Claudin-5 levels are specifically reduced in myocytes from a mouse model of muscular dystrophy with cardiomyopathy. To establish whether claudin-5 is similarly specifically reduced in human cardiomyopathy, we compared the levels of claudin-5 with other cell junction proteins in 62 cardiomyopathic end-stage explant samples. We show that claudin-5 levels are reduced in at least 60% of patient samples compared with non-failing controls. Importantly, claudin-5 reductions can be independent of connexin-43, a gap junction protein previously reported to be reduced in failing heart samples. Other cell junction proteins including α-catenin, β-catenin, γ-catenin, desmoplakin, and N-cadherin are reduced in only a small number of failing samples and only in combination with reduced claudin-5 or connexin-43 levels. We also show that reduced claudin-5 levels can be present independently from dystrophin alterations, which are known to be capable of causing and resulting from cardiomyopathy. These data are the first to show alterations of a tight junction protein in human cardiomyopathy samples and suggest that claudin-5 may participate in novel mechanisms in the pathway to end-stage heart failure.
Citation Information
Mays, Tessily; Binkley, Philip F.; Lesinski, Amanda; Doshi, Amit A.; Quaile, Michael P.; Margulies, Kenneth B.; Janssen, Paul M.L.; and Rafael-Fortney, Jill A.. 2008. Claudin-5 Levels Are Reduced in Human End-Stage Cardiomyopathy. Journal of Molecular and Cellular Cardiology. Vol.45(1). 81-87. https://doi.org/10.1016/j.yjmcc.2008.04.005 PMID: 18513742 ISSN: 0022-2828