Document Detail

Cardiac Rac1 overexpression in mice creates a substrate for atrial arrhythmias characterized by structural remodelling.
MedLine Citation:
PMID:  20211865     Owner:  NLM     Status:  MEDLINE    
AIMS: The small GTPase Rac1 seems to play a role in the pathogenesis of atrial fibrillation (AF). The aim of the present study was to characterize the effects of Rac1 overexpression on atrial electrophysiology. METHODS AND RESULTS: In mice with cardiac overexpression of constitutively active Rac1 (RacET), statin-treated RacET, and wild-type controls (age 6 months), conduction in the right and left atrium (RA and LA) was mapped epicardially. The atrial effective refractory period (AERP) was determined and inducibility of atrial arrhythmias was tested. Action potentials were recorded in isolated cells. Left ventricular function was measured by pressure-volume analysis. Five of 11 RacET hearts showed spontaneous or inducible atrial tachyarrhythmias vs. 0 of 9 controls (P < 0.05). In RacET, the P-wave duration was significantly longer (26.8 +/- 2.1 vs. 16.7 +/- 1.1 ms, P = 0.001) as was total atrial activation time (RA: 13.6 +/- 4.4 vs. 3.2 +/- 0.5 ms; LA: 7.1 +/- 1.2 vs. 2.2 +/- 0.3 ms, P < 0.01). Prolonged local conduction times occurred more often in RacET (RA: 24.4 +/- 3.8 vs. 2.7 +/- 2.1%; LA: 19.1 +/- 6.3 vs. 1.2 +/- 0.7%, P < 0.01). The AERP and action potential duration did not differ significantly between both groups. RacET demonstrated significant atrial fibrosis but only moderate systolic heart failure. RacET and statin-treated RacET were not significantly different regarding atrial electrophysiology. CONCLUSION: The substrate for atrial arrhythmias in mice with Rac1 overexpression is characterized by conduction disturbances and atrial fibrosis. Electrical remodelling (i.e. a shortening of AERP) does not play a role. Statin treatment cannot prevent the structural and electrophysiological effects of pronounced Rac1 overexpression in this model.
Jan-Christian Reil; Mathias Hohl; Martin Oberhofer; Andrey Kazakov; Lars Kaestner; Patrick Mueller; Oliver Adam; Christoph Maack; Peter Lipp; Christian Mewis; Maurits Allessie; Ulrich Laufs; Michael Böhm; Hans-Ruprecht Neuberger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-07
Journal Detail:
Title:  Cardiovascular research     Volume:  87     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-16     Completed Date:  2010-11-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  485-93     Citation Subset:  IM    
Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Kirrberger Strasse, Homburg/Saar D 66421, Germany.
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MeSH Terms
Action Potentials
Arrhythmias, Cardiac / enzymology*,  genetics,  pathology,  physiopathology
Atrial Function* / drug effects
Gene Expression Regulation
Heart Atria / drug effects,  enzymology*,  pathology,  physiopathology
Heart Conduction System / drug effects,  enzymology*,  pathology,  physiopathology
Heart Failure / enzymology,  pathology,  physiopathology
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
Mice, Transgenic
Time Factors
Ventricular Function, Left
Ventricular Pressure
rac1 GTP-Binding Protein / genetics,  metabolism*
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; EC GTP-Binding Protein

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

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