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Cellular remodeling in rapidly stimulated atrial myocytes and tissue
Author(s) -
Mace Lisa C,
Yi Yajun,
Hu Xinran,
Yang Zhenjiang,
Murray Katherine T.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a321-c
Subject(s) - atrial fibrillation , stimulation , tissue remodeling , myocyte , ventricular remodeling , ex vivo , medicine , in vivo , atrial myocytes , microbiology and biotechnology , heart failure , biology , inflammation
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the United States, where it remains a major cause of stroke and death. Nevertheless, current therapies are inadequate. The clinical course of AF is a progressive one, with cellular remodeling of the atria (reduced action potential duration [APD] and I Ca,L ) due to rapid activation, perpetuating the arrhythmia. The biologic processes that initiate remodeling are not currently known. Our goal is to identify the early molecular events that trigger cellular remodeling in response to rapid activation. We previously reported that mouse atrial tumor cells (HL‐1 cells) subjected to rapid stimulation demonstrated cellular remodeling, suggesting a myocyte‐specific response. To determine the relevance of these findings for larger mammals, canine atrial strips were stimulated ex vivo at either a physiological (1.5 Hz, control) or rapid (4.0 Hz) rate for up to 2 hr. APD was significantly reduced in rapidly stimulated atrial strips when compared to controls (90 min; P<0.05). To investigate the transcriptional modulation associated with the remodeling process, RNA was extracted from HL‐1 cells in the absence and presence of rapid stimulation and subjected to microarray analysis. For individual transcripts, as well as broad categories of genes grouped by functional classification, there was striking conservation between rapidly stimulated HL‐1 cells and human AF, with a number of novel features identified. Confirmation of results using real‐time quantitative RT‐PCR is underway, and specific agonists/inhibitors will be investigated to further explore the role of the implicated molecules and pathways in the remodeling process.