Cyclical stretch induces structural changes in atrial myocytes

Journal of Cellular and Molecular Medicine

Anne Margreet De Jong¹  Alexander H. Maass¹  Silke U. Oberdorf-Maass¹  Rudolf A. De Boer¹  Wiek H. Van Gilst¹ 

[1] Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

关键词: Atria;    stretch;    remodelling;    cell culture;   

DOI  :  10.1111/jcmm.12064

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 The Authors Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.