Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2016 Mar 1;109(3):345-7.
doi: 10.1093/cvr/cvw008. Epub 2016 Jan 17.

PITX2: a master regulator of cardiac channelopathy in atrial fibrillation?

Na Li  1 , Dobromir Dobrev  2 , Xander H T Wehrens  3
Affiliations
Editorial

PITX2: a master regulator of cardiac channelopathy in atrial fibrillation?

Na Li et al. Cardiovasc Res. .
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic representation of arrhythmic mechanisms associated with PITX2. In the prevailing model (left, Lozano-Velasco study), down-regulation of PITX2c (i) reduces the gene expression of α-subunit of L-type Ca2+ channel (ICa,L), a hallmark of electrical remodeling in AF (ii) increases the expression of Ca2+ handling proteins via Wnt signaling, which ultimately leads to Ca2+ overload in sarcoplasmic reticulum (SR). In an alternative model (right, Pérez-Hernández study), up-regulation of PITX2c, observed in chronic AF patients, can enhance the transcription of genes encoding the subunits of slow delayed rectifying K+ channel (IKs) and atrial natriuretic peptide (ANP). The latter is responsible for the augmented ICa,L in response to β-adrenergic stimulation. These cellular events will ultimately (i) promote the development of delayed afterdepolarizations (DADs), or (ii) abbreviate the action potential duration (APD), both of which are the well-established mechanisms contributing to pathogenesis of atrial fibrillation.
See this image and copyright information in PMC

Comment on

Similar articles

See all similar articles

Cited by

References

    1. Andrade J, Khairy P, Dobrev D, Nattel S. The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms. Circ Res 2014;114:1453–1468. - PubMed
    1. Gudbjartsson DF, Arnar DO, Helgadottir A, Gretarsdottir S, Holm H, Sigurdsson A, Jonasdottir A, Baker A, Thorleifsson G, Kristjansson K, Palsson A, Blondal T, Sulem P, Backman VM, Hardarson GA, Palsdottir E, Helgason A, Sigurjonsdottir R, Sverrisson JT, Kostulas K, Ng MC, Baum L, So WY, Wong KS, Chan JC, Furie KL, Greenberg SM, Sale M, Kelly P, MacRae CA, Smith EE, Rosand J, Hillert J, Ma RC, Ellinor PT, Thorgeirsson G, Gulcher JR, Kong A, Thorsteinsdottir U, Stefansson K. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature 2007;448:353–357. - PubMed
    1. Kaab S, Darbar D, van Noord C, Dupuis J, Pfeufer A, Newton-Cheh C, Schnabel R, Makino S, Sinner MF, Kannankeril PJ, Beckmann BM, Choudry S, Donahue BS, Heeringa J, Perz S, Lunetta KL, Larson MG, Levy D, MacRae CA, Ruskin JN, Wacker A, Schomig A, Wichmann HE, Steinbeck G, Meitinger T, Uitterlinden AG, Witteman JC, Roden DM, Benjamin EJ, Ellinor PT. Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation. Eur Heart J 2009;30:813–819. - PMC - PubMed
    1. Lubitz SA, Lunetta KL, Lin H, Arking DE, Trompet S, Li G, Krijthe BP, Chasman DI, Barnard J, Kleber ME, Dorr M, Ozaki K, Smith AV, Muller-Nurasyid M, Walter S, Agarwal SK, Bis JC, Brody JA, Chen LY, Everett BM, Ford I, Franco OH, Harris TB, Hofman A, Kaab S, Mahida S, Kathiresan S, Kubo M, Launer LJ, Macfarlane PW, Magnani JW, McKnight B, McManus DD, Peters A, Psaty BM, Rose LM, Rotter JI, Silbernagel G, Smith JD, Sotoodehnia N, Stott DJ, Taylor KD, Tomaschitz A, Tsunoda T, Uitterlinden AG, Van Wagoner DR, Volker U, Volzke H, Murabito JM, Sinner MF, Gudnason V, Felix SB, Marz W, Chung M, Albert CM, Stricker BH, Tanaka T, Heckbert SR, Jukema JW, Alonso A, Benjamin EJ, Ellinor PT. Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese. J Am Coll Cardiol 2014;63:1200–1210. - PMC - PubMed
    1. Ellinor PT, Lunetta KL, Albert CM, Glazer NL, Ritchie MD, Smith AV, Arking DE, Muller-Nurasyid M, Krijthe BP, Lubitz SA, Bis JC, Chung MK, Dorr M, Ozaki K, Roberts JD, Smith JG, Pfeufer A, Sinner MF, Lohman K, Ding J, Smith NL, Smith JD, Rienstra M, Rice KM, Van Wagoner DR, Magnani JW, Wakili R, Clauss S, Rotter JI, Steinbeck G, Launer LJ, Davies RW, Borkovich M, Harris TB, Lin H, Volker U, Volzke H, Milan DJ, Hofman A, Boerwinkle E, Chen LY, Soliman EZ, Voight BF, Li G, Chakravarti A, Kubo M, Tedrow UB, Rose LM, Ridker PM, Conen D, Tsunoda T, Furukawa T, Sotoodehnia N, Xu S, Kamatani N, Levy D, Nakamura Y, Parvez B, Mahida S, Furie KL, Rosand J, Muhammad R, Psaty BM, Meitinger T, Perz S, Wichmann HE, Witteman JC, Kao WH, Kathiresan S, Roden DM, Uitterlinden AG, Rivadeneira F, McKnight B, Sjogren M, Newman AB, Liu Y, Gollob MH, Melander O, Tanaka T, Stricker BH, Felix SB, Alonso A, Darbar D, Barnard J, Chasman DI, Heckbert SR, Benjamin EJ, Gudnason V, Kaab S. Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nat Genet 2012;44:670–675. - PMC - PubMed