Cyclical stretch induces structural changes in atrial myocytes

Anne Margreet De Jong, Alexander H. Maass*, Silke U. Oberdorf-Maass, Rudolf A. De Boer, Wiek H. Van Gilst, Isabelle C. Van Gelder

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

32 Citations (Scopus)

Abstract

Atrial fibrillation (AF) often occurs in the presence of an underlying disease. These underlying diseases cause atrial remodelling, which make the atria more susceptible to AF. Stretch is an important mediator in the remodelling process. The aim of this study was to develop an atrial cell culture model mimicking remodelling due to atrial pressure overload. Neonatal rat atrial cardiomyocytes (NRAM) were cultured and subjected to cyclical stretch on elastic membranes. Stretching with 1 Hz and 15% elongation for 30 min. resulted in increased expression of immediate early genes and phosphorylation of Erk and p38. A 24-hr stretch period resulted in hypertrophy-related changes including increased cell diameter, reinduction of the foetal gene program and cell death. No evidence of apoptosis was observed. Expression of atrial natriuretic peptide, brain natriuretic peptide and growth differentiation factor-15 was increased, and calcineurin signalling was activated. Expression of several potassium channels was decreased, suggesting electrical remodelling. Atrial stretch-induced change in skeletal α-actin expression was inhibited by pravastatin, but not by eplerenone or losartan. Stretch of NRAM results in elevation of stress markers, changes related to hypertrophy and dedifferentiation, electrical remodelling and cell death. This model can contribute to investigating the mechanisms involved in the remodelling process caused by stretch and to the testing of pharmaceutical agents.

Original languageEnglish
Pages (from-to)743-753
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume17
Issue number6
DOIs
Publication statusPublished - Jun 2013
Externally publishedYes

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