title: Cyclical stretch induces structural changes in atrial myocytes.
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.
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Anne Margreet
authors.initials: AM
authors.lastname: De Jong
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Maass
authors.forename: Silke U
authors.initials: SU
authors.lastname: Oberdorf-Maass
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: De Boer
authors.forename: Wiek H
authors.initials: WH
authors.lastname: Van Gilst
authors.forename: Isabelle C
authors.initials: IC
authors.lastname: Van Gelder
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009320:Atrial Natriuretic Factor / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D064752:Atrial Remodeling; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055436:Growth Differentiation Factor 15 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D017035:Pravastatin / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013314:Stress, Mechanical; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D000924:Anticholesteremic Agents; C526142:Gdf15 protein, rat; D055436:Growth Differentiation Factor 15; D015221:Potassium Channels; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019703:Calcineurin; D017035:Pravastatin