Abstract
The mature mammalian myocardium contains composite junctions (areae compositae) that comprise proteins of adherens junctions as well as desmosomes. Mutations or deficiency of many of these proteins are linked to heart failure and/or arrhythmogenic cardiomyopathy in patients. We firstly wanted to address the question whether the expression of these proteins shows an age-dependent alteration in the atrium of the human heart. Right atrial biopsies, obtained from patients undergoing routine bypass surgery for coronary heart disease were subjected to immunohistology and/or western blotting for the plaque proteins plakoglobin (γ-catenin) and plakophilin 2. Moreover, the Z-band protein cypher 1 (Cypher/ZASP) and calcium handling proteins of the sarcoplasmic reticulum (SR) like phospholamban, SERCA and calsequestrin were analyzed. We noted expression of plakoglobin, plakophilin 2 and Cypher/ZASP in these atrial preparations on western blotting and/or immunohistochemistry. There was an increase of Cypher/ZASP expression with age. The present data extend our knowledge on the expression of anchoring proteins and SR regulatory proteins in the atrium of the human heart and indicate an age-dependent variation in protein expression. It is tempting to speculate that increased expression of Cypher/ZASP may contribute to mechanical changes in the aging human myocardium.
Highlights
Aging represents an important risk factor for the development of cardiovascular diseases like heart failure
Mutations of plakophilin 2 are often found in patients with arrhythmogenic right ventricular dysplasia/ cardiomyopathy (ARVD/C), which eventually can result in heart failure[4]
There were no significant differences between the groups with respect to plakophilin
Summary
Aging represents an important risk factor for the development of cardiovascular diseases like heart failure. For the structural integrity of the heart, junctional proteins are highly relevant[1] Their mutations or altered expression levels can lead to cardiac malformations, development of heart failure and cardiac arrhythmias. In this work we focused on, firstly, plakophilin 2, secondly, plakoglobin which both are important linker molecules that connect members of the cadherin family of transmembrane proteins with the cytoskeleton and, thirdly, a structural protein of high cardiac relevance located to the Z discs called ZASP. Genetic ablation of plakophilin 2 in mice is lethal and impairs the formation of appropriate cardiac ventricles[5] Another junctional protein of interest in this context is plakoglobin. Cytoskeleton[6,7] It is of importance for proper cardiac function because, for instance, in homozygous knockout mice a rupture of cardiac ventricles was noted that was embryonically lethal[8]. A progress report of this work has appeared in abstract form[21]
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