RT Journal Article
T1 Pitx2c increases in atrial myocytes from chronic atrial fibrillation patients enhancing IKs and decreasing ICa,L
A1 Pérez Hernández, Marta
A1 Matamoros, Marcos
A1 Barana Muñoz, Adriana
A1 Amorós García, Irene
A1 Gómez García, Ricardo
A1 Núñez, Mercedes
A1 Sacristán, Sandra
A1 Pinto, Ángel
A1 Fernández-Avilés Díaz, Francisco Jesús
A1 Tamargo Menéndez, Juan
A1 Delpón Mosquera, María Eva
A1 Caballero Collado, Ricardo
AB Aims: Atrial fibrillation (AF) produces rapid changes in the electrical properties of the atria (electrical remodelling) that promote its own recurrence. In chronic AF (CAF) patients, up-regulation of the slow delayed rectifier K(+) current (IKs) and down-regulation of the voltage-gated Ca(2+) current (ICa,L) are hallmarks of electrical remodelling and critically contribute to the abbreviation of action potential duration and atrial refractory period. Recent evidences suggested that Pitx2c, a bicoid-related homeodomain transcription factor involved in directing cardiac asymmetric morphogenesis, could play a role in atrial remodelling. However, its effects on IKs and ICa,L are unknown.Methods and results: Real-time quantitative polymerase chain reaction analysis showed that Pitx2c mRNA expression was significantly higher in human atrial myocytes from CAF patients than those from sinus rhythm patients. The expression of Pitx2c was positively and negatively correlated with IKs and ICa,L densities, respectively. Expression of Pitx2c in HL-1 cells increased IKs density and reduced ICa,L density. Luciferase assays demonstrated that Pitx2c increased transcriptional activity of KCNQ1 and KCNE1 genes. Conversely, its effects on ICa,L could be mediated by the atrial natriuretic peptide.Conclusion: Our results demonstrated for the first time that CAF increases Pitx2c expression in isolated human atrial myocytes and suggested that this transcription factor could contribute to the CAF-induced IKs increase and ICa,L reduction observed in humans.
PB European Society of Cardiology
SN 0008-6363
YR 2016
FD 2016
LK https://hdl.handle.net/20.500.14352/92052
UL https://hdl.handle.net/20.500.14352/92052
LA eng
NO Pérez-Hernández, M., Matamoros, M., Barana, A., Amorós, I., Gómez, R., Núñez, M., Sacristán, S., Pinto, Á., Fernández-Avilés, F., Tamargo, J., Delpón, E., Caballero, R., 2016. Pitx2c increases in atrial myocytes from chronic atrial fibrillation patients enhancingIKsand decreasingICa,L. Cardiovascular Research 109, 431–441.. https://doi.org/10.1093/cvr/cvv280
NO Centro Nacional de Investigaciones Cardiovasculares
NO Ministerio de Ciencia e Innovación (España)
NO Instituto de Salud Carlos III
NO Comunidad Autónoma de Madrid
NO Fundación Mutua Madrileña
NO Fundación BBVA
DS Docta Complutense
RD 13 abr 2026