RUJA: Repositorio Institucional de Producción Científica

 

PITX2 Insufficiency Leads to Atrial Electrical and Structural Remodeling Linked to Arrhythmogenesis

dc.contributor.authorChinchilla, Ana
dc.contributor.authorDaimi, Houria
dc.contributor.authorLozano-Velasco, Estefanía
dc.contributor.authorDomínguez-Macías, Jorge Nicolás
dc.contributor.authorCaballero-Collado, Ricardo
dc.contributor.authorDelpón, Eva
dc.contributor.authorTamargo, Juan
dc.contributor.authorCinca, Juan
dc.contributor.authorHove-Madsen, Leif
dc.contributor.authorAránega, Amelia Eva
dc.contributor.authorFranco, Diego
dc.date.accessioned2025-01-16T10:03:55Z
dc.date.available2025-01-16T10:03:55Z
dc.date.issued2011-04-21
dc.description.abstractBackground: 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 evidence 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: 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 electric function, the insufficiency of which results in cellular and molecular changes leading to atrial electric and structural remodeling linked to arrhythmogenesis.es_ES
dc.description.sponsorshipVI European Union Integrated Project “Heart Failure and Cardiac Repair” LSHM-CT-2005-018630; Junta de Andalucía CTS-1614; Junta de Andalucía (CTS-03878); Ministerio de Innovación y Ciencia MICINN BFU2009-11566, MICINN BFU-2008-01217. REDINSCOR (RD006/0003/0000), CNIC translational CNIC 2009/08; Ministerio de Salud y Consumo PI08/665 and HERACLES RD06/009 network; Ministerio de Ciencia y educación SAF2008-04903; UJA2009/12/11es_ES
dc.identifier.citationChinchilla A, Daimi H, Lozano-Velasco E, Dominguez JN, Caballero R, Delpón E, Tamargo J, Cinca J, Hove-Madsen L, Aranega AE, Franco D. PITX2 insufficiency leads to atrial electrical and structural remodeling linked to arrhythmogenesis. Circ Cardiovasc Genet. 2011 Jun;4(3):269-79. doi: 10.1161/CIRCGENETICS.110.958116. Epub 2011 Apr 21. PMID: 21511879.es_ES
dc.identifier.issn1942-325Xes_ES
dc.identifier.other10.1161/CIRCGENETICS.110.958116es_ES
dc.identifier.urihttps://www.ahajournals.org/doi/10.1161/CIRCGENETICS.110.958116?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmedes_ES
dc.identifier.urihttps://hdl.handle.net/10953/4012
dc.publisherAmerican Heart Associationes_ES
dc.relation.ispartofCirc Cardiovasc Genet, 2011, Jun;4(3):269-79es_ES
dc.rightsCC0 1.0 Universal*
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.subjectPitx2es_ES
dc.subjectArrhythmiaes_ES
dc.subjectAtrial Fibrillationes_ES
dc.subjectGene regulationes_ES
dc.subjectPolymorphismes_ES
dc.subjectTranscription factorses_ES
dc.titlePITX2 Insufficiency Leads to Atrial Electrical and Structural Remodeling Linked to Arrhythmogenesises_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersiones_ES

Archivos

Bloque original

Mostrando 1 - 2 de 2
Cargando...
Miniatura
Nombre:
Chinchilla 2011 Circ Cardv Genet 2011 Supp.pdf
Tamaño:
163.42 KB
Formato:
Adobe Portable Document Format
Descripción:
Material Suplemebtario
Cargando...
Miniatura
Nombre:
Chinchilla 2011 Circ Cardv Genet 2011.pdf
Tamaño:
2.9 MB
Formato:
Adobe Portable Document Format
Descripción:
Artículo Original

Bloque de licencias

Mostrando 1 - 1 de 1
No hay miniatura disponible
Nombre:
license.txt
Tamaño:
1.98 KB
Formato:
Item-specific license agreed upon to submission
Descripción:

Colecciones