Gap junction remodelling by chronic pressure overload is related to the increased susceptibility to atrial fibrillation in rat heart

Seung Yong Shin, Won-Min Jo, Too Jae Min, Byoung Kwon Kim, Dae Hyun Song, Seong Hyeop Hyeon, Jee Eun Kwon, Wang Soo Lee, Kwang Je Lee, Sang Wook Kim, Tae Ho Kim, Chee Jeong Kim, Sung Il Im, Hong Euy Lim

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Aims Left atrial (LA) fibrosis caused by various pathological stimuli is a common finding. However, the difference of atrial remodelling via haemodynamic change in diverse cardiomyopathy has not been elucidated. Methods and results Male Sprague-Dawley rats (6-8 weeks, n = 180) were randomly assigned to three groups and corresponding sham control groups: (i) ischaemic cardiomyopathy, (ii) left ventricular hypertrophy (LVH), and (iii) dilated cardiomyopathy. At 12 weeks after operation, atrial fibrillation (AF) inducibility and duration were assessed by in vivo burst transoesophageal pacing. Using the Langendorff apparatus, left ventricular (LV) function and pressure were measured. The expression of connexin-43 (Cx43) and alpha-smooth muscle actin (α-SMA) in atrial tissues was assessed by quantitative real-time polymerase chain reaction and immunohistochemical staining. Fibrosis was analysed by Masson's trichrome staining. Compared with controls, the LA weight/heart weight ratio was increased in the LVH group alone, and was significantly correlated with AF duration (P < 0.001, R = 0.388). Atrial fibrillation inducibility and duration were higher and longer only in the LVH group (P = 0.002, 0.079, respectively), and isolated LV diastolic dysfunction and elevated LV pressure were observed. Although α-SMA expression and fibrosis were increased in all three cardiomyopathy models, down-regulation of Cx43 expression in the LA was observed in the LVH group alone. Conclusion Chronic pressure overload in the absence of LV systolic dysfunction resulted in LA hypertrophy and increased susceptibility to AF, which might be related to conduction abnormality via decreased expression and lateral distribution of Cx43 as well as interstitial fibrosis.

Original languageEnglish
Pages (from-to)655-663
Number of pages9
JournalEuropace
Volume17
Issue number4
DOIs
Publication statusPublished - 2015 Apr 1

Fingerprint

Gap Junctions
Left Ventricular Hypertrophy
Atrial Fibrillation
Connexin 43
Fibrosis
Cardiomyopathies
Pressure
Left Ventricular Dysfunction
Ventricular Pressure
Atrial Remodeling
Staining and Labeling
Weights and Measures
Dilated Cardiomyopathy
Left Ventricular Function
Hypertrophy
Smooth Muscle
Sprague Dawley Rats
Actins
Real-Time Polymerase Chain Reaction
Down-Regulation

Keywords

  • Atrial fibrillation
  • Connexin
  • Fibroblast
  • Fibrosis
  • Gap junction
  • Hypertrophy
  • Pressure overload
  • Remodelling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Gap junction remodelling by chronic pressure overload is related to the increased susceptibility to atrial fibrillation in rat heart. / Shin, Seung Yong; Jo, Won-Min; Min, Too Jae; Kim, Byoung Kwon; Song, Dae Hyun; Hyeon, Seong Hyeop; Kwon, Jee Eun; Lee, Wang Soo; Lee, Kwang Je; Kim, Sang Wook; Kim, Tae Ho; Kim, Chee Jeong; Im, Sung Il; Lim, Hong Euy.

In: Europace, Vol. 17, No. 4, 01.04.2015, p. 655-663.

Research output: Contribution to journalArticle

Shin, SY, Jo, W-M, Min, TJ, Kim, BK, Song, DH, Hyeon, SH, Kwon, JE, Lee, WS, Lee, KJ, Kim, SW, Kim, TH, Kim, CJ, Im, SI & Lim, HE 2015, 'Gap junction remodelling by chronic pressure overload is related to the increased susceptibility to atrial fibrillation in rat heart', Europace, vol. 17, no. 4, pp. 655-663. https://doi.org/10.1093/europace/euu294
Shin, Seung Yong ; Jo, Won-Min ; Min, Too Jae ; Kim, Byoung Kwon ; Song, Dae Hyun ; Hyeon, Seong Hyeop ; Kwon, Jee Eun ; Lee, Wang Soo ; Lee, Kwang Je ; Kim, Sang Wook ; Kim, Tae Ho ; Kim, Chee Jeong ; Im, Sung Il ; Lim, Hong Euy. / Gap junction remodelling by chronic pressure overload is related to the increased susceptibility to atrial fibrillation in rat heart. In: Europace. 2015 ; Vol. 17, No. 4. pp. 655-663.
@article{885f4ce562b744eba8d9f696e945b660,
title = "Gap junction remodelling by chronic pressure overload is related to the increased susceptibility to atrial fibrillation in rat heart",
abstract = "Aims Left atrial (LA) fibrosis caused by various pathological stimuli is a common finding. However, the difference of atrial remodelling via haemodynamic change in diverse cardiomyopathy has not been elucidated. Methods and results Male Sprague-Dawley rats (6-8 weeks, n = 180) were randomly assigned to three groups and corresponding sham control groups: (i) ischaemic cardiomyopathy, (ii) left ventricular hypertrophy (LVH), and (iii) dilated cardiomyopathy. At 12 weeks after operation, atrial fibrillation (AF) inducibility and duration were assessed by in vivo burst transoesophageal pacing. Using the Langendorff apparatus, left ventricular (LV) function and pressure were measured. The expression of connexin-43 (Cx43) and alpha-smooth muscle actin (α-SMA) in atrial tissues was assessed by quantitative real-time polymerase chain reaction and immunohistochemical staining. Fibrosis was analysed by Masson's trichrome staining. Compared with controls, the LA weight/heart weight ratio was increased in the LVH group alone, and was significantly correlated with AF duration (P < 0.001, R = 0.388). Atrial fibrillation inducibility and duration were higher and longer only in the LVH group (P = 0.002, 0.079, respectively), and isolated LV diastolic dysfunction and elevated LV pressure were observed. Although α-SMA expression and fibrosis were increased in all three cardiomyopathy models, down-regulation of Cx43 expression in the LA was observed in the LVH group alone. Conclusion Chronic pressure overload in the absence of LV systolic dysfunction resulted in LA hypertrophy and increased susceptibility to AF, which might be related to conduction abnormality via decreased expression and lateral distribution of Cx43 as well as interstitial fibrosis.",
keywords = "Atrial fibrillation, Connexin, Fibroblast, Fibrosis, Gap junction, Hypertrophy, Pressure overload, Remodelling",
author = "Shin, {Seung Yong} and Won-Min Jo and Min, {Too Jae} and Kim, {Byoung Kwon} and Song, {Dae Hyun} and Hyeon, {Seong Hyeop} and Kwon, {Jee Eun} and Lee, {Wang Soo} and Lee, {Kwang Je} and Kim, {Sang Wook} and Kim, {Tae Ho} and Kim, {Chee Jeong} and Im, {Sung Il} and Lim, {Hong Euy}",
year = "2015",
month = "4",
day = "1",
doi = "10.1093/europace/euu294",
language = "English",
volume = "17",
pages = "655--663",
journal = "Europace",
issn = "1099-5129",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Gap junction remodelling by chronic pressure overload is related to the increased susceptibility to atrial fibrillation in rat heart

AU - Shin, Seung Yong

AU - Jo, Won-Min

AU - Min, Too Jae

AU - Kim, Byoung Kwon

AU - Song, Dae Hyun

AU - Hyeon, Seong Hyeop

AU - Kwon, Jee Eun

AU - Lee, Wang Soo

AU - Lee, Kwang Je

AU - Kim, Sang Wook

AU - Kim, Tae Ho

AU - Kim, Chee Jeong

AU - Im, Sung Il

AU - Lim, Hong Euy

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Aims Left atrial (LA) fibrosis caused by various pathological stimuli is a common finding. However, the difference of atrial remodelling via haemodynamic change in diverse cardiomyopathy has not been elucidated. Methods and results Male Sprague-Dawley rats (6-8 weeks, n = 180) were randomly assigned to three groups and corresponding sham control groups: (i) ischaemic cardiomyopathy, (ii) left ventricular hypertrophy (LVH), and (iii) dilated cardiomyopathy. At 12 weeks after operation, atrial fibrillation (AF) inducibility and duration were assessed by in vivo burst transoesophageal pacing. Using the Langendorff apparatus, left ventricular (LV) function and pressure were measured. The expression of connexin-43 (Cx43) and alpha-smooth muscle actin (α-SMA) in atrial tissues was assessed by quantitative real-time polymerase chain reaction and immunohistochemical staining. Fibrosis was analysed by Masson's trichrome staining. Compared with controls, the LA weight/heart weight ratio was increased in the LVH group alone, and was significantly correlated with AF duration (P < 0.001, R = 0.388). Atrial fibrillation inducibility and duration were higher and longer only in the LVH group (P = 0.002, 0.079, respectively), and isolated LV diastolic dysfunction and elevated LV pressure were observed. Although α-SMA expression and fibrosis were increased in all three cardiomyopathy models, down-regulation of Cx43 expression in the LA was observed in the LVH group alone. Conclusion Chronic pressure overload in the absence of LV systolic dysfunction resulted in LA hypertrophy and increased susceptibility to AF, which might be related to conduction abnormality via decreased expression and lateral distribution of Cx43 as well as interstitial fibrosis.

AB - Aims Left atrial (LA) fibrosis caused by various pathological stimuli is a common finding. However, the difference of atrial remodelling via haemodynamic change in diverse cardiomyopathy has not been elucidated. Methods and results Male Sprague-Dawley rats (6-8 weeks, n = 180) were randomly assigned to three groups and corresponding sham control groups: (i) ischaemic cardiomyopathy, (ii) left ventricular hypertrophy (LVH), and (iii) dilated cardiomyopathy. At 12 weeks after operation, atrial fibrillation (AF) inducibility and duration were assessed by in vivo burst transoesophageal pacing. Using the Langendorff apparatus, left ventricular (LV) function and pressure were measured. The expression of connexin-43 (Cx43) and alpha-smooth muscle actin (α-SMA) in atrial tissues was assessed by quantitative real-time polymerase chain reaction and immunohistochemical staining. Fibrosis was analysed by Masson's trichrome staining. Compared with controls, the LA weight/heart weight ratio was increased in the LVH group alone, and was significantly correlated with AF duration (P < 0.001, R = 0.388). Atrial fibrillation inducibility and duration were higher and longer only in the LVH group (P = 0.002, 0.079, respectively), and isolated LV diastolic dysfunction and elevated LV pressure were observed. Although α-SMA expression and fibrosis were increased in all three cardiomyopathy models, down-regulation of Cx43 expression in the LA was observed in the LVH group alone. Conclusion Chronic pressure overload in the absence of LV systolic dysfunction resulted in LA hypertrophy and increased susceptibility to AF, which might be related to conduction abnormality via decreased expression and lateral distribution of Cx43 as well as interstitial fibrosis.

KW - Atrial fibrillation

KW - Connexin

KW - Fibroblast

KW - Fibrosis

KW - Gap junction

KW - Hypertrophy

KW - Pressure overload

KW - Remodelling

UR - http://www.scopus.com/inward/record.url?scp=84926653460&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84926653460&partnerID=8YFLogxK

U2 - 10.1093/europace/euu294

DO - 10.1093/europace/euu294

M3 - Article

C2 - 25398404

AN - SCOPUS:84926653460

VL - 17

SP - 655

EP - 663

JO - Europace

JF - Europace

SN - 1099-5129

IS - 4

ER -