@article{3091278,
    title = "Remodeling of myocyte gap junctions in arrhythmogenic right ventricular
cardiomyopathy due to a deletion in plakoglobin (Naxos disease)",
    author = "Kaplan, SR and Gard, JJ and Protonotarios, N and Tsatsopoulou, A and and Spiliopoulou, C and Anastasakis, A and Squarcioni, CP and McKenna, WJ and and Thiene, G and Basso, C and Brousse, N and Fontaine, G and Saffitz, and JE",
    journal = "Heart Rhythm",
    year = "2004",
    volume = "1",
    number = "1",
    pages = "3-11",
    publisher = "EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC",
    issn = "1547-5271",
    doi = "10.1016/j.hrthm.2004.01.001",
    keywords = "arrhythmia; cardiomyopathy; cell adhesion; molecules;
immunohistochemistry",
    abstract = "OBJECTIVES We tested the hypothesis that defective interactions between
adhesion junctions and the cytoskeleton caused by the plakoglobin
mutation in Naxos disease lead to remodeling of gap junctions and
altered expression of the major gap junction protein, connexin43.
BACKGROUND Naxos disease, a recessive form of arrhythmogenic right
ventricular cardiomyopathy, is associated with a high incidence of
arrhythmias and sudden cardiac death. Naxos disease is caused by a
mutation in plakoglobin, a protein that links cell-cell adhesion
molecules to the cytoskeleton.
METHODS Myocardial expression of connexin43 and other intercellular
junction proteins was characterized in 4 patients with Naxos disease.
Immunohistochemistry was performed in all 4 patients, and immunoblotting
and electron microscopy were performed in 1 patient who died in
childhood before overt arrhythmogenic right ventricular cardiomyopathy
had developed.
RESULTS Connexin43 expression at intercellular junctions was reduced
significantly in both right and left ventricles in all patients with
Naxos disease. Electron microscopy revealed smaller and fewer gap
junctions interconnecting ventricular myocytes. Mutant plakoglobin was
expressed but failed to localize normally at intercellular junctions.
Localization of N-cadherin, alpha- and beta-catenins, plakophilin-2,
desmoplakin-1, and desmocollin-2 at intercalated disks appeared normal.
CONCLUSIONS Remodeling of gap junctions occurs early in Naxos disease,
presumably because of abnormal linkage between mechanical junctions and
the cytoskeleton. Gap junction remodeling may produce a coupling defect
which, combined with the subsequent development of pathologic changes in
myocardium, could contribute to a highly arrhythmogenic substrate and
enhance the risk of sudden death in Naxos disease. (C) 2004 Elsevier
Inc. All rights reserved."
}