Age-related regulation and region-specific distribution of ion channel subunits promoting atrial fibrillation in human left and right atria

Peter Biliczki; Reinier A Boon; Zenawit Girmatsion; Alicia Bukowska; Balázs Ördög; Bernhard M Kaess; Stefan H Hohnloser; Andreas Goette; András Varró; Anton Moritz; Stanley Nattel; Joachim R Ehrlich

doi:https://doi.org/10.1093/europace/euz135

Age-related regulation and region-specific distribution of ion channel subunits promoting atrial fibrillation in human left and right atria

Peter Biliczki, Reinier A Boon, Zenawit Girmatsion, Alicia Bukowska, Balázs Ördög, Bernhard M Kaess, Stefan H Hohnloser, Andreas Goette, András Varró, Anton Moritz, Stanley Nattel, Joachim R Ehrlich

Research output: Contribution to journal › Article › Academic › peer-review

19 Citations (Scopus)

Abstract

AIMS : Age-induced changes and electrical remodelling are important components of the atrial fibrillation (AF) substrate. To study regional distribution and age-dependent changes in gene expression that may promote AF in human atria.

METHODS AND RESULTS : Human left atrial (LA) and right atrial (RA) tissue samples were obtained from donor hearts unsuitable for transplantation and from patients undergoing mitral valve repair. Atrial fibrillation was mimicked in vitro by tachypacing of human atrial tissue slices. Ionic currents were studied by the whole-cell patch-clamp technique; gene expression was analysed by real-time qPCR and immunoblotting. Both healthy RA and RA from older patients showed greater CACNA1c mRNA and CaV1.2 protein expression than LA. No age-dependent changes of Kir2.1 expression in both atria were seen. Remodelling occurred in a qualitatively similar manner in RA and LA. IK1 and Kir2.1 protein expression increased with AF. MiR-1, miR-26a, and miR-26b were down-regulated with AF in both atria. ICa,L was decreased. CACNA1c and CACNA2b expression decreased and miR-328 increased in RA and LA during AF. Ex vivo tachypacing of human atrial slices replicated these findings. There were age-dependent increases in miR-1 and miR-328, while miR-26a decreased with age in atrial tissues from healthy human donor hearts.

CONCLUSION : Features of electrical remodelling in man occur in a qualitatively similar manner in both human atria. Age-related miR-328 dysregulation and reduced ICa,L may contribute to increased AF susceptibility with age.

Original language	English
Pages (from-to)	1261-1269
Number of pages	9
Journal	Europace
Volume	21
Issue number	8
DOIs	https://doi.org/10.1093/europace/euz135
Publication status	Published - 1 Aug 2019

Access to Document

https://doi.org/10.1093/europace/euz135

Cite this

Biliczki, P., Boon, R. A., Girmatsion, Z., Bukowska, A., Ördög, B., Kaess, B. M., Hohnloser, S. H., Goette, A., Varró, A., Moritz, A., Nattel, S., & Ehrlich, J. R. (2019). Age-related regulation and region-specific distribution of ion channel subunits promoting atrial fibrillation in human left and right atria. Europace, 21(8), 1261-1269. https://doi.org/10.1093/europace/euz135

@article{1b06f85f935a4523a49601ad28fde128,

title = "Age-related regulation and region-specific distribution of ion channel subunits promoting atrial fibrillation in human left and right atria",

abstract = "AIMS : Age-induced changes and electrical remodelling are important components of the atrial fibrillation (AF) substrate. To study regional distribution and age-dependent changes in gene expression that may promote AF in human atria.METHODS AND RESULTS : Human left atrial (LA) and right atrial (RA) tissue samples were obtained from donor hearts unsuitable for transplantation and from patients undergoing mitral valve repair. Atrial fibrillation was mimicked in vitro by tachypacing of human atrial tissue slices. Ionic currents were studied by the whole-cell patch-clamp technique; gene expression was analysed by real-time qPCR and immunoblotting. Both healthy RA and RA from older patients showed greater CACNA1c mRNA and CaV1.2 protein expression than LA. No age-dependent changes of Kir2.1 expression in both atria were seen. Remodelling occurred in a qualitatively similar manner in RA and LA. IK1 and Kir2.1 protein expression increased with AF. MiR-1, miR-26a, and miR-26b were down-regulated with AF in both atria. ICa,L was decreased. CACNA1c and CACNA2b expression decreased and miR-328 increased in RA and LA during AF. Ex vivo tachypacing of human atrial slices replicated these findings. There were age-dependent increases in miR-1 and miR-328, while miR-26a decreased with age in atrial tissues from healthy human donor hearts.CONCLUSION : Features of electrical remodelling in man occur in a qualitatively similar manner in both human atria. Age-related miR-328 dysregulation and reduced ICa,L may contribute to increased AF susceptibility with age.",

author = "Peter Biliczki and Boon, {Reinier A} and Zenawit Girmatsion and Alicia Bukowska and Bal{\'a}zs {\"O}rd{\"o}g and Kaess, {Bernhard M} and Hohnloser, {Stefan H} and Andreas Goette and Andr{\'a}s Varr{\'o} and Anton Moritz and Stanley Nattel and Ehrlich, {Joachim R}",

year = "2019",

month = aug,

day = "1",

doi = "https://doi.org/10.1093/europace/euz135",

language = "English",

volume = "21",

pages = "1261--1269",

journal = "Europace",

issn = "1099-5129",

publisher = "Oxford University Press",

number = "8",

}

Biliczki, P, Boon, RA, Girmatsion, Z, Bukowska, A, Ördög, B, Kaess, BM, Hohnloser, SH, Goette, A, Varró, A, Moritz, A, Nattel, S & Ehrlich, JR 2019, 'Age-related regulation and region-specific distribution of ion channel subunits promoting atrial fibrillation in human left and right atria', Europace, vol. 21, no. 8, pp. 1261-1269. https://doi.org/10.1093/europace/euz135

TY - JOUR

T1 - Age-related regulation and region-specific distribution of ion channel subunits promoting atrial fibrillation in human left and right atria

AU - Biliczki, Peter

AU - Boon, Reinier A

AU - Girmatsion, Zenawit

AU - Bukowska, Alicia

AU - Ördög, Balázs

AU - Kaess, Bernhard M

AU - Hohnloser, Stefan H

AU - Goette, Andreas

AU - Varró, András

AU - Moritz, Anton

AU - Nattel, Stanley

AU - Ehrlich, Joachim R

PY - 2019/8/1

Y1 - 2019/8/1

N2 - AIMS : Age-induced changes and electrical remodelling are important components of the atrial fibrillation (AF) substrate. To study regional distribution and age-dependent changes in gene expression that may promote AF in human atria.METHODS AND RESULTS : Human left atrial (LA) and right atrial (RA) tissue samples were obtained from donor hearts unsuitable for transplantation and from patients undergoing mitral valve repair. Atrial fibrillation was mimicked in vitro by tachypacing of human atrial tissue slices. Ionic currents were studied by the whole-cell patch-clamp technique; gene expression was analysed by real-time qPCR and immunoblotting. Both healthy RA and RA from older patients showed greater CACNA1c mRNA and CaV1.2 protein expression than LA. No age-dependent changes of Kir2.1 expression in both atria were seen. Remodelling occurred in a qualitatively similar manner in RA and LA. IK1 and Kir2.1 protein expression increased with AF. MiR-1, miR-26a, and miR-26b were down-regulated with AF in both atria. ICa,L was decreased. CACNA1c and CACNA2b expression decreased and miR-328 increased in RA and LA during AF. Ex vivo tachypacing of human atrial slices replicated these findings. There were age-dependent increases in miR-1 and miR-328, while miR-26a decreased with age in atrial tissues from healthy human donor hearts.CONCLUSION : Features of electrical remodelling in man occur in a qualitatively similar manner in both human atria. Age-related miR-328 dysregulation and reduced ICa,L may contribute to increased AF susceptibility with age.

AB - AIMS : Age-induced changes and electrical remodelling are important components of the atrial fibrillation (AF) substrate. To study regional distribution and age-dependent changes in gene expression that may promote AF in human atria.METHODS AND RESULTS : Human left atrial (LA) and right atrial (RA) tissue samples were obtained from donor hearts unsuitable for transplantation and from patients undergoing mitral valve repair. Atrial fibrillation was mimicked in vitro by tachypacing of human atrial tissue slices. Ionic currents were studied by the whole-cell patch-clamp technique; gene expression was analysed by real-time qPCR and immunoblotting. Both healthy RA and RA from older patients showed greater CACNA1c mRNA and CaV1.2 protein expression than LA. No age-dependent changes of Kir2.1 expression in both atria were seen. Remodelling occurred in a qualitatively similar manner in RA and LA. IK1 and Kir2.1 protein expression increased with AF. MiR-1, miR-26a, and miR-26b were down-regulated with AF in both atria. ICa,L was decreased. CACNA1c and CACNA2b expression decreased and miR-328 increased in RA and LA during AF. Ex vivo tachypacing of human atrial slices replicated these findings. There were age-dependent increases in miR-1 and miR-328, while miR-26a decreased with age in atrial tissues from healthy human donor hearts.CONCLUSION : Features of electrical remodelling in man occur in a qualitatively similar manner in both human atria. Age-related miR-328 dysregulation and reduced ICa,L may contribute to increased AF susceptibility with age.

U2 - https://doi.org/10.1093/europace/euz135

DO - https://doi.org/10.1093/europace/euz135

M3 - Article

C2 - 31131392

SN - 1099-5129

VL - 21

SP - 1261

EP - 1269

JO - Europace

JF - Europace

IS - 8

ER -