Document Detail

Atrial cardiomyocyte tachycardia alters cardiac fibroblast function: a novel consideration in atrial remodeling.
MedLine Citation:
PMID:  17720149     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Atrial fibrillation (AF) causes tachycardia-induced atrial electrical remodeling, contributing to the progressive nature of the arrhythmia. Ventricular dysfunction due to a rapid response to AF can cause structural remodeling, but whether AF itself directly promotes atrial fibrosis is controversial. This study investigated the hypothesis that rapid atrial cardiomyocyte activation produces factors that influence atrial fibroblast proliferation and secretory functions. METHODS: Cultured canine atrial fibroblasts were treated with medium from rapidly-paced atrial cardiomyocytes, non-paced cardiomyocytes and cardiomyocyte-pacing medium only, and analyzed by [(3)H]thymidine incorporation, Western blot and real-time RT-PCR. RESULTS: Rapidly-paced cardiomyocyte-conditioned medium reduced [(3)H]thymidine uptake compared to non-paced cardiomyocyte-conditioned medium and medium alone (approximately 85%, P<0.01). Rapidly-paced cardiomyocyte medium increased alpha SMA protein (approximately 55%, p<0.001), collagen-1 (approximately 85%, P<0.05) and fibronectin-1 (approximately 205%, P<0.05) mRNA expression vs. controls. The angiotensin-1 receptor blocker valsartan attenuated pacing-induced alpha SMA changes but did not affect fibroblast proliferation. Suppression of contraction with blebbistatin did not prevent tachypacing-induced changes in [(3)H]thymidine uptake or alpha SMA upregulation, pointing to a primary role of electrical over mechanical cardiomyocyte activity. Atrial tissue from 1-week atrial-tachypaced dogs with ventricular rate control similarly showed upregulation of alpha SMA protein (approximately 40%, P<0.05), collagen-1 (approximately 380%, P<0.01) and fibronectin-1 (approximately 430%, P<0.001) mRNA versus shams. CONCLUSIONS: Rapidly-paced cardiomyocytes release substances that profoundly alter cardiac fibroblast function, inducing an activated myofibroblast phenotype that is reflected by increased ECM-gene expression in vivo. These findings are consistent with recent observations that AF per se may cause ECM remodeling, and have potentially important consequences for understanding and preventing the mechanisms underlying AF progression.
Brett Burstein; Xiao-Yan Qi; Yung-Hsin Yeh; Angelino Calderone; Stanley Nattel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-25
Journal Detail:
Title:  Cardiovascular research     Volume:  76     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-05     Completed Date:  2009-03-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  442-52     Citation Subset:  IM    
Department of Medicine, Montreal Heart Institute and Université de Montréal, Montreal, Canada.
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MeSH Terms
Actins / metabolism
Angiotensin II Type 1 Receptor Blockers / pharmacology
Atrial Fibrillation / physiopathology*
Cell Communication / physiology*
Cell Proliferation / drug effects
Cells, Cultured
Collagen Type I / metabolism
Culture Media / pharmacology
Disease Models, Animal
Extracellular Matrix / metabolism
Fibroblasts / cytology,  drug effects,  physiology*
Fibronectins / metabolism
Heterocyclic Compounds with 4 or More Rings / pharmacology
Muscle Contraction / drug effects
Myocytes, Cardiac / drug effects,  pathology,  physiology*
Tachycardia / physiopathology*
Tetrazoles / pharmacology
Valine / analogs & derivatives,  pharmacology
Ventricular Remodeling / physiology
Reg. No./Substance:
0/Actins; 0/Angiotensin II Type 1 Receptor Blockers; 0/Collagen Type I; 0/Culture Media; 0/Fibronectins; 0/Heterocyclic Compounds with 4 or More Rings; 0/Tetrazoles; 0/blebbistatin; 137862-53-4/valsartan; 7004-03-7/Valine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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