Tachycardia of atrial myocytes induces collagen expression in atrial fibroblasts through transforming growth factor β1

Chia Ti Tsai, Chuen Den Tseng, Juey Jen Hwang, Cho Kai Wu, Chih Chieh Yu, Yi Chih Wang, Wen Pin Chen, Ling Ping Lai, Fu Tien Chiang, Jiunn Lee Lin

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Aims: We investigated the molecular mechanism of rapid-depolarization- induced atrial fibrosis. Methods and results: We used a direct atrial myocyte-fibroblast contact co-culture and a fibroblast-specific transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF) and procollagen type I α-1 (COL1A1) luciferase reporter system to investigate the possible molecular mechanism of rapid-depolarization-induced atrial fibrosis. Mouse atrial fibroblasts were first transfected with promoter-luciferase reporters, and then co-cultured with HL-1 atrial myocytes. Rapid depolarization of atrial myocytes by rapid electrical field stimulation induced increased TGF-β1, CTGF and COL1A1 promoter activities in the co-cultured atrial fibroblasts (2.4 ± 0.3-fold increase, P = 0.008 for TGF-β1; 2.9 ± 0.4-fold increase, P < 0.001 for CTGF; and 2.1 ± 0.2-fold increase, P = 0.008 for COL1A1). Rapid depolarization of atrial myocytes increased paracrine secretion of angiotensin II (Ang II) and reactive oxygen species in the co-culture medium. Rapid electrical field stimulation-induced ROS generation in atrial myocytes was attenuated by the membrane NADPH oxidase inhibitor, apocynin. Atrial myocyte-induced expression of TGF-β1, CTGF and COL1A1 in atrial fibroblasts was attenuated by co-treatment with the Ang II receptor blocker, losartan, and apocynin. Atrial myocyte-induced COL1A1 expression in atrial fibroblasts was attenuated by anti-TGF-β1 antibody and RNA interference knockdown of the TGF-β1 receptor. Conclusion: We first demonstrated that tachycardia of atrial myocytes induced paracrine secretion of Ang II and reactive oxygen species, which in turn induced expression of CTGF and procollagen in co-cultured atrial fibroblasts through increasing TGF-β1 expression. The results may imply that use of an Ang II receptor blocker, in combination with an anti-oxidant, blocks rapid-depolarization-induced atrial fibrosis. Published on behalf of the European Society of Cardiology. All rights reserved.

Original languageEnglish
Pages (from-to)805-815
Number of pages11
JournalCardiovascular Research
Volume89
Issue number4
DOIs
Publication statusPublished - Mar 1 2011
Externally publishedYes

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Transforming Growth Factors
Tachycardia
Muscle Cells
Connective Tissue Growth Factor
Collagen
Fibroblasts
Fibrosis
Angiotensin Receptor Antagonists
Coculture Techniques
Luciferases
Angiotensin II
Electric Stimulation
Reactive Oxygen Species
Procollagen
Losartan
Growth Factor Receptors
NADPH Oxidase
Collagen Type I
RNA Interference
Oxidants

Keywords

  • Angiotensin II
  • Atrial fibrillation
  • Contact co-culture
  • Procollagen
  • Rapid depolarization
  • Reactive oxygen species
  • Transforming growth factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Tachycardia of atrial myocytes induces collagen expression in atrial fibroblasts through transforming growth factor β1. / Tsai, Chia Ti; Tseng, Chuen Den; Hwang, Juey Jen; Wu, Cho Kai; Yu, Chih Chieh; Wang, Yi Chih; Chen, Wen Pin; Lai, Ling Ping; Chiang, Fu Tien; Lin, Jiunn Lee.

In: Cardiovascular Research, Vol. 89, No. 4, 01.03.2011, p. 805-815.

Research output: Contribution to journalArticle

Tsai, CT, Tseng, CD, Hwang, JJ, Wu, CK, Yu, CC, Wang, YC, Chen, WP, Lai, LP, Chiang, FT & Lin, JL 2011, 'Tachycardia of atrial myocytes induces collagen expression in atrial fibroblasts through transforming growth factor β1', Cardiovascular Research, vol. 89, no. 4, pp. 805-815. https://doi.org/10.1093/cvr/cvq322
Tsai, Chia Ti ; Tseng, Chuen Den ; Hwang, Juey Jen ; Wu, Cho Kai ; Yu, Chih Chieh ; Wang, Yi Chih ; Chen, Wen Pin ; Lai, Ling Ping ; Chiang, Fu Tien ; Lin, Jiunn Lee. / Tachycardia of atrial myocytes induces collagen expression in atrial fibroblasts through transforming growth factor β1. In: Cardiovascular Research. 2011 ; Vol. 89, No. 4. pp. 805-815.
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AU - Yu, Chih Chieh

AU - Wang, Yi Chih

AU - Chen, Wen Pin

AU - Lai, Ling Ping

AU - Chiang, Fu Tien

AU - Lin, Jiunn Lee

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N2 - Aims: We investigated the molecular mechanism of rapid-depolarization- induced atrial fibrosis. Methods and results: We used a direct atrial myocyte-fibroblast contact co-culture and a fibroblast-specific transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF) and procollagen type I α-1 (COL1A1) luciferase reporter system to investigate the possible molecular mechanism of rapid-depolarization-induced atrial fibrosis. Mouse atrial fibroblasts were first transfected with promoter-luciferase reporters, and then co-cultured with HL-1 atrial myocytes. Rapid depolarization of atrial myocytes by rapid electrical field stimulation induced increased TGF-β1, CTGF and COL1A1 promoter activities in the co-cultured atrial fibroblasts (2.4 ± 0.3-fold increase, P = 0.008 for TGF-β1; 2.9 ± 0.4-fold increase, P < 0.001 for CTGF; and 2.1 ± 0.2-fold increase, P = 0.008 for COL1A1). Rapid depolarization of atrial myocytes increased paracrine secretion of angiotensin II (Ang II) and reactive oxygen species in the co-culture medium. Rapid electrical field stimulation-induced ROS generation in atrial myocytes was attenuated by the membrane NADPH oxidase inhibitor, apocynin. Atrial myocyte-induced expression of TGF-β1, CTGF and COL1A1 in atrial fibroblasts was attenuated by co-treatment with the Ang II receptor blocker, losartan, and apocynin. Atrial myocyte-induced COL1A1 expression in atrial fibroblasts was attenuated by anti-TGF-β1 antibody and RNA interference knockdown of the TGF-β1 receptor. Conclusion: We first demonstrated that tachycardia of atrial myocytes induced paracrine secretion of Ang II and reactive oxygen species, which in turn induced expression of CTGF and procollagen in co-cultured atrial fibroblasts through increasing TGF-β1 expression. The results may imply that use of an Ang II receptor blocker, in combination with an anti-oxidant, blocks rapid-depolarization-induced atrial fibrosis. Published on behalf of the European Society of Cardiology. All rights reserved.

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KW - Angiotensin II

KW - Atrial fibrillation

KW - Contact co-culture

KW - Procollagen

KW - Rapid depolarization

KW - Reactive oxygen species

KW - Transforming growth factor

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