The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Pitx2 prevents susceptibility to atrial arrhythmias by inhibiting left-sided pacemaker specification
Open accessAbstract
Atrial fibrillation (AF), the most prevalent sustained cardiac arrhythmia, often coexists with the related arrhythmia atrial flutter (AFL). Limitations in effectiveness and safety of current therapies make an understanding of the molecular mechanism underlying AF more urgent. Genome-wide association studies implicated a region of human chromosome 4q25 in familial AF and AFL, ≈150 kb distal to the Pitx2 homeobox gene, a developmental left–right asymmetry (LRA) gene. To investigate the significance of the 4q25 variants, we used mouse models to investigate Pitx2 in atrial arrhythmogenesis directly. When challenged by programmed stimulation, Pitx2 null+/− adult mice had atrial arrhythmias, including AFL and atrial tachycardia, indicating that Pitx2 haploinsufficiency predisposes to atrial arrhythmias. Microarray and in situ studies indicated that Pitx2 suppresses sinoatrial node (SAN)-specific gene expression, including Shox2 , in the left atrium of embryos and young adults. In vivo ChIP and transfection experiments indicated that Pitx2 directly bound Shox2 in vivo, supporting the notion that Pitx2 directly inhibits the SAN-specific genetic program in left atrium. Our findings implicate Pitx2 and Pitx2 -mediated LRA-signaling pathways in prevention of atrial arrhythmias.
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Cites
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
A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke
Gudbjartsson, D. F., Holm, H., Gretarsdottir, S., Thorleifsson, G., Walters, G. B., Thorgeirsson, G., Gulcher, J., Mathiesen, E. B., Njølstad, I., Nyrnes, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.417 · Cited by 489
Cited by
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
Calkins, 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
Calkins, 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
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 Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezw313 · Cited by 1,403
Pitx2 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
Self-citation
Metadata
- Authors
- Wang, J., Klysik, E., Sood, S., Johnson, R. L., Wehrens, X. H. T., & Martin, J. F.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2010-05-10
- Volume
- 107
- Issue
- 21
- Pages
- 9753-9758
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2087818666
- Cited by
- 320
- References
- 2
- FWCI
- 14.51
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Pitx2 prevents susceptibility to atrial arrhythmias by inhibiting left-sided pacemaker specification. https://app.cochat.ai/papers/10.1073/pnas.0912585107
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- Wang, J., Klysik, E., Sood, S., Johnson, R. L., Wehrens, X. H. T., & Martin, J. F. (2010). Pitx2 prevents susceptibility to atrial arrhythmias by inhibiting left-sided pacemaker specification. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0912585107
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
