Claudin-5 levels are reduced in human end-stage cardiomyopathy.
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 alpha-catenin, beta-catenin, gamma-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.
Mays
Tessily A
TA
Department of Molecular and Cellular Biochemistry, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
Binkley
Philip F
PF
Lesinski
Amanda
A
Doshi
Amit A
AA
Quaile
Michael P
MP
Margulies
Kenneth B
KB
Janssen
Paul M L
PM
Rafael-Fortney
Jill A
JA
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D009202:Cardiomyopathies / Q000378:metabolism* / Q000473:pathology; D051177:Catenins / Q000378:metabolism; D062507:Claudin-5; D018031:Connexin 43; D051180:Desmoplakins / Q000378:metabolism; D005260:Female; D017629:Gap Junctions / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D019108:Tight Junctions / Q000378:metabolism* / Q000473:pathology
D015703:Antigens, CD; C050361:CDH2 protein, human; C107466:CLDN5 protein, human; D015820:Cadherins; D051177:Catenins; D062507:Claudin-5; D018031:Connexin 43; D051180:Desmoplakins; C500216:GJA1 protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins