Long-standing arterial hypertension is associated with Pitx2 down-regulation in a rat model of spontaneous atrial tachyarrhythmias

被引：17

作者：

Scridon, Alina ^{[1
,2
]}

Fouilloux-Meugnier, Emmanuelle ^{[3
]}

Loizon, Emmanuelle ^{[3
]}

Rome, Sophie ^{[3
]}

Julien, Claude ^{[2
]}

Barres, Christian ^{[2
]}

Chevalier, Philippe ^{[2
,4
]}

机构：

[1] Univ Med & Pharm Tirgu Mures, Dept Physiol, Targu Mures 540139, Romania

[2] Univ Lyon 1, EA 4612, Unite Neurocardiol, F-69008 Lyon, France

[3] Univ Lyon 1, INSERM CarMen U1060, F-69008 Lyon, France

[4] Hop Louis Pradel, Hosp Civils Lyon, Serv Rythmol, F-69500 Bron, France

来源：

EUROPACE | 2015年 / 17卷 / 01期

关键词：

Atrial tachyarrhythmia; Experimental model; Transcriptomics; Pitx2; Hypertension; CHROMOSOME; 4Q25; GENE-EXPRESSION; FIBRILLATION; VARIANTS; SUSCEPTIBILITY; ZFHX3; RISK;

D O I：

10.1093/europace/euu139

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims The timecourse of left atrial Pitx2 down-regulation in the setting of atrial tachyarrhythmias remains unknown. Accordingly, we aimed to assess the age dependency of left atrial Pitx2 expression in an experimental model of spontaneous atrial tachyarrhythmias in rats. Methods and results Atrial sampling was performed in three groups (n = 4 each) of young (14-week-old), adult (24-week-old), and ageing (48-week-old) spontaneously hypertensive rats (SHRs), in which we previously demonstrated the age dependency of spontaneous atrial tachyarrhythmias, and three groups (n = 4 each) of age-matched normotensive Wistar-Kyoto (WKY) rats. mRNA expression of Pitx2 was studied using real-time polymerase chain reaction. Ageing SHRs presented significantly lower left atrial Pitx2 expressions compared with age-matched WKY rats (P = 0.02), while no significant difference was observed between young or adult SHRs and age-matched WKY rats (both P > 0.05). Among SHRs, Pitx2 expressions showed a progressive, age-dependent decrease (34.9 +/- 6.7 in young SHRs, 17.1 +/- 3.6 in adult SHRs, and 10.7 +/- 1.7 in ageing SHRs, P = 0.04) and were significantly negatively correlated with both age (Spearman r = -0.86, P < 0.01) and heart weight (Spearman r = -0.76, P < 0.01). Conclusion The present study suggests the presence of age-dependent left atrial Pitx2 down-regulation in SHRs. The strong negative correlation between left atrial Pitx2 expression and heart weight among SHRs may indicate a link between long-standing arterial hypertension and Pitx2-related atrial arrhythmogenicity.

引用

页码：160 / 165

页数：6

共 25 条

[1]

Ausma J, 1997, AM J PATHOL, V151, P985

[2] Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry [J].

Benjamin, Emelia J. ;

Rice, Kenneth M. ;

Arking, Dan E. ;

Pfeufer, Arne ;

van Noord, Charlotte ;

Smith, Albert V. ;

Schnabel, Renate B. ;

Bis, Joshua C. ;

Boerwinkle, Eric ;

Sinner, Moritz F. ;

Dehghan, Abbas ;

Lubitz, Steven A. ;

D'Agostino, Ralph B., Sr. ;

Lumley, Thomas ;

Ehret, Georg B. ;

Heeringa, Jan ;

Aspelund, Thor ;

Newton-Cheh, Christopher ;

Larson, Martin G. ;

Marciante, Kristin D. ;

Soliman, Elsayed Z. ;

Rivadeneira, Fernando ;

Wang, Thomas J. ;

Eiriksdottir, Gudny ;

Levy, Daniel ;

Psaty, Bruce M. ;

Li, Man ;

Chamberlain, Alanna M. ;

Hofman, Albert ;

Vasan, Ramachandran S. ;

Harris, Tamara B. ;

Rotter, Jerome I. ;

Kao, W. H. Linda ;

Agarwal, Sunil K. ;

Stricker, Bruno H. Ch ;

Wang, Ke ;

Launer, Lenore J. ;

Smith, Nicholas L. ;

Chakravarti, Aravinda ;

Uitterlinden, Andre G. ;

Wolf, Philip A. ;

Sotoodehnia, Nona ;

Koettgen, Anna ;

van Duijn, Cornelia M. ;

Meitinger, Thomas ;

Mueller, Martina ;

Perz, Siegfried ;

Steinbeck, Gerhard ;

Wichmann, H-Erich ;

Lunetta, Kathryn L. .

NATURE GENETICS, 2009, 41 (08) :879-881

[3] Mutational analysis of the PITX2 and NKX2-5 genes in patients with idiopathic atrial fibrillation [J].

Boldt, Leif-Hendrik ;

Posch, Maximilian G. ;

Perrot, Andreas ;

Polotzki, Michael ;

Rolf, Sascha ;

Parwani, Abdul S. ;

Huemer, Martin ;

Wutzler, Alexander ;

Oezcelik, Cemil ;

Haverkamp, Wilhelm .

INTERNATIONAL JOURNAL OF CARDIOLOGY, 2010, 145 (02) :316-317

[4] Activation of the calcineurin signaling pathway induces atrial hypertrophy during atrial fibrillation [J].

Bukowska, A ;

Lendeckel, U ;

Hirte, D ;

Wolke, C ;

Striggow, F ;

Röhnert, P ;

Huth, C ;

Klein, HU ;

Goette, A .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2006, 63 (03) :333-342

[5] PITX2 Insufficiency Leads to Atrial Electrical and Structural Remodeling Linked to Arrhythmogenesis [J].

Chinchilla, Ana ;

Daimi, Houria ;

Lozano-Velasco, Estefania ;

Dominguez, Jorge N. ;

Caballero, Ricardo ;

Delpon, Eva ;

Tamargo, Juan ;

Cinca, Juan ;

Hove-Madsen, Leif ;

Aranega, Amelia E. ;

Franco, Diego .

CIRCULATION-CARDIOVASCULAR GENETICS, 2011, 4 (03) :269-U133

[6] Increased susceptibility to atrial tachyarrhythmia in spontaneously hypertensive rat hearts [J].

Choisy, Stephanie C. M. ;

Arberry, Lesley A. ;

Hancox, Jules C. ;

James, Andrew F. .

HYPERTENSION, 2007, 49 (03) :498-505

[7] Prevalence of atrial fibrillation in the general population and in high-risk groups: the ECHOES study [J].

Davis, Russell C. ;

Hobbs, F. D. Richard ;

Kenkre, Joyce E. ;

Roalfe, Andrea K. ;

Iles, Rachel ;

Lip, Gregory Y. H. ;

Davies, Michael K. .

EUROPACE, 2012, 14 (11) :1553-1559

[8] Common variants in KCNN3 are associated with lone atrial fibrillation [J].

Ellinor, Patrick T. ;

Lunetta, Kathryn L. ;

Glazer, Nicole L. ;

Pfeufer, Arne ;

Alonso, Alvaro ;

Chung, Mina K. ;

Sinner, Moritz F. ;

de Bakker, Paul I. W. ;

Mueller, Martina ;

Lubitz, Steven A. ;

Fox, Ervin ;

Darbar, Dawood ;

Smith, Nicholas L. ;

Smith, Jonathan D. ;

Schnabel, Renate B. ;

Soliman, Elsayed Z. ;

Rice, Kenneth M. ;

Van Wagoner, David R. ;

Beckmann, Britt-M ;

van Noord, Charlotte ;

Wang, Ke ;

Ehret, Georg B. ;

Rotter, Jerome I. ;

Hazen, Stanley L. ;

Steinbeck, Gerhard ;

Smith, Albert V. ;

Launer, Lenore J. ;

Harris, Tamara B. ;

Makino, Seiko ;

Nelis, Mari ;

Milan, David J. ;

Perz, Siegfried ;

Esko, Tonu ;

Koettgen, Anna ;

Moebus, Susanne ;

Newton-Cheh, Christopher ;

Li, Man ;

Moehlenkamp, Stefan ;

Wang, Thomas J. ;

Kao, W. H. Linda ;

Vasan, Ramachandran S. ;

Noethen, Markus M. ;

MacRae, Calum A. ;

Stricker, Bruno H. Ch ;

Hofman, Albert ;

Uitterlinden, Andre G. ;

Levy, Daniel ;

Boerwinkle, Eric ;

Metspalu, Andres ;

Topol, Eric J. .

NATURE GENETICS, 2010, 42 (03) :240-U36

[9] Variants conferring risk of atrial fibrillation on chromosome 4q25 [J].

Gudbjartsson, Daniel F. ;

Arnar, David O. ;

Helgadottir, Anna ;

Gretarsdottir, Solveig ;

Holm, Hilma ;

Sigurdsson, Asgeir ;

Jonasdottir, Adalbjorg ;

Baker, Adam ;

Thorleifsson, Gudmar ;

Kristjansson, Kristleifur ;

Palsson, Arnar ;

Blondal, Thorarinn ;

Sulem, Patrick ;

Backman, Valgerdur M. ;

Hardarson, Gudmundur A. ;

Palsdottir, Ebba ;

Helgason, Agnar ;

Sigurjonsdottir, Runa ;

Sverrisson, Jon T. ;

Kostulas, Konstantinos ;

Ng, Maggie C. Y. ;

Baum, Larry ;

So, Wing Yee ;

Wong, Ka Sing ;

Chan, Juliana C. N. ;

Furie, Karen L. ;

Greenberg, Steven M. ;

Sale, Michelle ;

Kelly, Peter ;

MacRae, Calum A. ;

Smith, Eric E. ;

Rosand, Jonathan ;

Hillert, Jan ;

Ma, Ronald C. W. ;

Ellinor, Patrick T. ;

Thorgeirsson, Gudmundur ;

Gulcher, Jeffrey R. ;

Kong, Augustine ;

Thorsteinsdottir, Unnur ;

Stefansson, Kari .

NATURE, 2007, 448 (7151) :353-357

[10] A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke [J].

Gudbjartsson, Daniel F. ;

Holm, Hilma ;

Gretarsdottir, Solveig ;

Thorleifsson, Gudmar ;

Walters, G. Bragi ;

Thorgeirsson, Gudmundur ;

Gulcher, Jeffrey ;

Mathiesen, Ellisiv B. ;

Njolstad, Inger ;

Nyrnes, Audhild ;

Wilsgaard, Tom ;

Hald, Erin M. ;

Hveem, Kristian ;

Stoltenberg, Camilla ;

Kucera, Gayle ;

Stubblefield, Tanya ;

Carter, Shannon ;

Roden, Dan ;

Ng, Maggie C. Y. ;

Baum, Larry ;

So, Wing Yee ;

Wong, Ka Sing ;

Chan, Juliana C. N. ;

Gieger, Christian ;

Wichmann, H-Erich ;

Gschwendtner, Andreas ;

Dichgans, Martin ;

Kuhlenbaeumer, Gregor ;

Berger, Klaus ;

Ringelstein, E. Bernd ;

Bevan, Steve ;

Markus, Hugh S. ;

Kostulas, Konstantinos ;

Hillert, Jan ;

Sveinbjornsdottir, Sigurlaug ;

Valdimarsson, Einar M. ;

Lochen, Maja-Lisa ;

Ma, Ronald C. W. ;

Darbar, Dawood ;

Kong, Augustine ;

Arnar, David O. ;

Thorsteinsdottir, Unnur ;

Stefansson, Kari .

NATURE GENETICS, 2009, 41 (08) :876-878

← 1 2 3 →