Document Detail


PITX2 Insufficiency Leads to Atrial Electrical and Structural Remodeling Linked to Arrhythmogenesis.
MedLine Citation:
PMID:  21511879     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: -Pitx2 is a homeobox transcription factor that plays a pivotal role in early left/right determination during embryonic development. Pitx2 loss-of-function mouse mutants display early embryonic lethality with severe cardiac malformations, demonstrating the importance of Pitx2 during cardiogenesis. Recently, independent genome-wide association studies have provided new evidences for a putative role of PITX2 in the adult heart. These studies have independently reported several risk variants close to the PITX2 locus on chromosome 4q25 that are strongly associated with atrial fibrillation in humans. METHODS AND RESULTS: -Here we show for the first time that PITX2C expression is significantly decreased in human patients with sustained atrial fibrillation, thus providing a molecular link between PITX2 loss-of-function and atrial fibrillation. In addition, morphological, molecular and electrophysiological characterization of chamber-specific Pitx2 conditional mouse mutants reveals that atrial, but not ventricular, chamber-specific deletion of Pitx2 results in differences in the action potential amplitude and resting membrane potential in the adult heart as well as ECG characteristics of atrioventricular block. Lack of Pitx2 in atrial myocardium impairs sodium channel and potassium channel expression, mediated in part by miRNA misexpression. CONCLUSIONS: -This study thus identifies Pitx2 as an upstream transcriptional regulator of atrial electrical function, insufficiency of which results in cellular and molecular changes leading to atrial electrical and structural remodeling linked to arrhythmogenesis.
Authors:
Ana Chinchilla; Houria Daimi; Estefanía Lozano-Velasco; Jorge N Dominguez; Ricardo Caballero; Eva Delpón; Juan Tamargo; Juan Cinca; Leif Hove-Madsen; Amelia E Aranega; Diego Franco
Related Documents :
12035039 - Ventricular reconstruction results in improved left ventricular function and ameliorati...
11930339 - Differential diagnosis of infective endocarditis.
21074539 - Inhibition of p53 after acute myocardial infarction: reduction of apoptosis is countera...
20299349 - Percutaneous mitral valve repair with the mitraclip system: acute results from a real w...
10221399 - Mitral valve replacement through a giant left atrial appendage.
16684059 - Triangular resection and folding of posterior leaflet for mitral valve repair.
12035039 - Ventricular reconstruction results in improved left ventricular function and ameliorati...
2368679 - Detection and assessment of severity of tricuspid regurgitation using first-pass radion...
18596109 - Central a1-receptor activation associated with onset of torpor protects the heart again...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-21
Journal Detail:
Title:  Circulation. Cardiovascular genetics     Volume:  -     ISSN:  1942-3268     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101489144     Medline TA:  Circ Cardiovasc Genet     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 University of Jaén, Jaén, Spain;
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

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


Previous Document:  Common genetic variants, QT interval, and sudden cardiac death in a Finnish population-based study.
Next Document:  The HSP90 molecular chaperone cycle regulates cyclical transcriptional dynamics of the glucocorticoi...