Abstract 12180: Structural Changes Caused by Stretch in a Primary Atrial Cell Culture Model Mimicking Atrial Structural Remodeling Occurring Before the Onset of Atrial Fibrillation
Introduction: Atrial fibrillation (AF) occurs mostly in the presence of a substrate, e.g. caused by hypertension. Before the first AF episode structural remodeling occurs, which deteriorates once AF develops. Stretch is an important mediator in this remodeling process. Our goal is to develop an atrial cell culture model mimicking atrial remodeling in pressure overload of the atria, representing the atrial situation after start of hypertension but before the first episode of AF.
Methods: Neonatal rat atrial cardiomyocytes (NRAM) were cultured and set under cyclical stretch on elastic membranes. Cells were analyzed after 3–24hr of stretch. mRNA levels of alpha and beta-myosin heavy chain (MHC) and skeletal alpha-actin were used as markers of dedifferentiation. Breakdown of troponin T protein was used as a measure of myolysis. Expression of stress markers, such as ANP, BNP and growth differentiation factor-15 (GDF15) were also determined after stretching and after 24hr stimulation with the alpha-adrenergic agonist phenylephrine (PE).
Results: Stretching with 1Hz and 15% elongation for 24hr showed 1.8-fold increased beta/alpha-MHC ratio. In addition, skeletal alpha-actin expression was 1.5 fold increased after 6hr of stretch. Stretching with 1Hz and 15% elongation or 3Hz and 10% elongation did not reduce troponin T protein expression. ANP mRNA levels were unchanged after stretch with 1Hz and 15% elongation, but ANP was released into the cell culture medium. BNP and GDF-15 mRNA levels were 2-fold increased after 3hr and 1.4-fold after 24hr, respectively. PE stimulation did not induce ANP and GDF-15 mRNA expression in NRAM, but BNP expression was 1.7-fold increased. In contrast, in neonatal rat ventricular myocytes (NRVM) ANP expression was 5-fold increased upon 24hr stretch with 1Hz and 15% elongation and 4.9 fold upon stimulation with PE.
Conclusions: Stretch of neonatal rat atrial cardiomyocytes results in cellular changes which may resemble those seen before AF, such as dedifferentiation and changes in expression of natriuretic peptides, but not myolysis. This model can be a way of testing new or known pharmaceutical agents in order to ultimately prevent AF.
- © 2010 by American Heart Association, Inc.