Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare form of cardiomyopathy in which the heart muscle of the right ventricle is replaced by fatty or fibrous tissue. The right ventricle is then unable to contract properly and the heart's ability to pump blood is weakened, often resulting in an abnormal heart rhythm, cardiac arrest or death. In a study appearing in the July issue of the Journal of Clinical Investigation, Ali Marian and colleagues from Baylor College of Medicine show that cardiac myocyte-specific loss of a protein called desmoplakin in mice causes the protein plakoglobin to be relocated to the nucleus of these cells, upregulation of the expression of genes involved in fat cell formation and the subsequent accumulation of fat droplets in heart muscle, myocyte apoptosis, and cardiac arrhythmias similar to human ARVC. The study provides a novel molecular mechanism for how this disease develops and an animal model of human ARVC for future study.
In an accompanying commentary, Ludwig Thierfelder and colleagues from the Max Delbruck Center for Molecular Medicine, Berlin, discuss the signaling pathways involved in this disease and how they manifest their effects on heart cell differentiation and physiology.
TITLE: Suppression of canonical Wnt/b-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy
AUTHOR CONTACT:
Ali J. Marian
Baylor College of Medicine, Houston, Texas, USA.
E-mail: amarianbcm.tmc.
View the PDF of this article at: https://the-jci/article.php?id=27751
ACCOMPANYING COMMENTARY
TITLE: Arrhythmogenic right ventricular cardiomyopathy: moving toward mechanism
AUTHOR CONTACT:
Ludwig Thierfelder
Max Delbruck Center for Molecular Medicine, Berlin, Germany.
Email: lthiermdc-berlin.de.
AUTHOR CONTACT:
Calum A. MacRae
Massachusetts General Hospital, Charlestown, Massachusetts, USA.
Email: macraecvrc.mgh.harvard.
View the PDF of this article at: https://the-jci/article.php?id=29174
JCI table of contents: July 3, 2006
Contact: Brooke Grindlinger
Journal of Clinical Investigation