The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
PITX2c Is Expressed in the Adult Left Atrium, and Reducing Pitx2c Expression Promotes Atrial Fibrillation Inducibility and Complex Changes in Gene Expression
Open accessAbstract
Background—: Intergenic variations on chromosome 4q25, close to the PITX2 transcription factor gene, are associated with atrial fibrillation (AF). We therefore tested whether adult hearts express PITX2 and whether variation in expression affects cardiac function. Methods and Results—: mRNA for PITX2 isoform c was expressed in left atria of human and mouse, with levels in right atrium and left and right ventricles being 100-fold lower. In mice heterozygous for Pitx2c ( Pitx2c +/− ), left atrial Pitx2c expression was 60% of wild-type and cardiac morphology and function were not altered, except for slightly elevated pulmonary flow velocity. Isolated Pitx2 c +/− hearts were susceptible to AF during programmed stimulation. At short paced cycle lengths, atrial action potential durations were shorter in Pitx2c +/− than in wild-type. Perfusion with the β-receptor agonist orciprenaline abolished inducibility of AF and reduced the effect on action potential duration. Spontaneous heart rates, atrial conduction velocities, and activation patterns were not affected in Pitx2c +/− hearts, suggesting that action potential duration shortening caused wave length reduction and inducibility of AF. Expression array analyses comparing Pitx2c +/− with wild-type, for left atrial and right atrial tissue separately, identified genes related to calcium ion binding, gap and tight junctions, ion channels, and melanogenesis as being affected by the reduced expression of Pitx2c. Conclusions—: These findings demonstrate a physiological role for PITX2 in the adult heart and support the hypothesis that dysregulation of PITX2 expression can be responsible for susceptibility to AF.
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Stewart, S., Hart, C. L., Hole, D. J., & McMurray, J. J. V. (2002) · The American Journal of Medicine · doi:10.1016/s0002-9343(02)01236-6 · Cited by 1,562
Variants conferring risk of atrial fibrillation on chromosome 4q25
Gudbjartsson, D. F., Arnar, D. O., Helgadottir, A., Gretarsdottir, S., Holm, H., Sigurdsson, A., Jonasdottir, A., Baker, A., Thorleifsson, G., Kristjansson, K., et al. (2007) · Nature · doi:10.1038/nature06007 · Cited by 955
An atlas of combinatorial transcriptional regulation in mouse and man
Ravasi, T., Suzuki, H., Cannistraci, C. V., Katayama, S., Bajic, V. B., Tan, K., Akalin, A., Schmeier, S., Kanamori-Katayama, M., Bertin, N., et al. (2010) · Cell · doi:10.1016/j.cell.2010.01.044 · Cited by 715
Kirchhof, P., Bax, J., Blomstrom-Lundquist, C., Calkins, H., Camm, A. J., Cappato, R., Cosio, F., Crijns, H., Diener, H.-C., Goette, A., et al. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp235 · Cited by 202
Self-citationMelanocyte-like cells in the heart and pulmonary veins contribute to atrial arrhythmia triggers
Levin, M. D., Lu, M. M., Petrenko, N. B., Hawkins, B. J., Gupta, T. H., Lang, D., Buckley, P. T., Jochems, J., Liu, F., Spurney, C. F., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39109 · Cited by 92
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2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw210 · Cited by 6,418
Self-citationCalkins, H., Kuck, K. H., Cappato, R., Brugada, J., Camm, A. J., Chen, S.-A., Crijns, H. J. G., Damiano, R. J., Davies, D. W., DiMarco, J., et al. (2012) · Europace · doi:10.1093/europace/eus027 · Cited by 2,722
Self-citationCalkins, H., Kuck, K. H., Cappato, R., Brugada, J., Camm, A. J., Chen, S.-A., Crijns, H. J. G., Damiano, R. J., Davies, D. W., DiMarco, J., et al. (2012) · Heart Rhythm · doi:10.1016/j.hrthm.2011.12.016 · Cited by 1,456
Self-citation2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezw313 · Cited by 1,403
Self-citationPitx2 promotes heart repair by activating the antioxidant response after cardiac injury
Tao, G., Kahr, P. C., Morikawa, Y., Zhang, M., Rahmani, M., Heallen, T. R., Li, L., Sun, Z., Olson, E. N., Amendt, B. A., et al. (2016) · Nature · doi:10.1038/nature17959 · Cited by 283
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Metadata
- Authors
- Kirchhof, P., Kahr, P. C., Kaese, S., Piccini, I., Vokshi, I., Scheld, H.-H., Rotering, H., Fortmueller, L., Laakmann, S., Verheule, S., Schotten, U., Fabritz, L., & Brown, N. A.
- Venue
- Circulation: Cardiovascular Genetics
- Published
- 2011-04
- Volume
- 4
- Issue
- 2
- Pages
- 123-133
- ISSN
- 1942-325X (ISSN-L)
- 1942-3268
- OpenAlex
- W1988891936
- Cited by
- 309
- References
- 5
- FWCI
- 16.20
- Type
- journal article
- Language
- en
- Open access
- green
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- Kirchhof, P., Kahr, P. C., Kaese, S., Piccini, I., Vokshi, I., Scheld, H.-H., Rotering, H., Fortmueller, L., Laakmann, S., Verheule, S., Schotten, U., Fabritz, L., & Brown, N. A. (2011). PITX2c Is Expressed in the Adult Left Atrium, and Reducing Pitx2c Expression Promotes Atrial Fibrillation Inducibility and Complex Changes in Gene Expression. Circulation: Cardiovascular Genetics. https://doi.org/10.1161/circgenetics.110.958058
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