21 Citations (Scopus)

Abstract

Background: Androgen deficiency produces heart failure, which can be ameliorated by testosterone supplementation. Cardiac fibrosis plays a critical role in the pathophysiology of heart failure. This study aimed to evaluate whether testosterone can attenuate cardiac fibroblast activity through modulating transforming growth factor (TGF)-β and angiotensin (Ang) II signaling. Methods:Migration, proliferation, myofibroblast differentiation, collagen production, and transcription signaling were evaluated in adult male rat (weighing 300-350 g) cardiac fibroblasts with and without incubation with testosterone (10 nM) and co-administration of TGF-β1 (10 ng/ml) or Ang II (100 nM) by cell migration analysis, proliferation assay, soluble collagenmeasurement, zymographic analysis, immunofluorescence microscopy, realtime PCR and Western blot. Results: Compared to thosewithout testosterone, testosterone-treated fibroblasts exhibited less collagen production. Testosterone-treated fibroblasts also had less migration, proliferation, myofibroblast differentiation, and collagen production in the presence of TGF-β1, or had less collagen production with Ang II. Testosteronetreated fibroblasts had decreased phosphorylated Akt, mammalian target of rapamycin, and 4E binding protein-1 irrespective of TGF-β1 treatment and had increased matrix metalloproteinase (MMP)-2 in the presence of TGF-β1 treatment, and had decreased phosphorylated P38 and Smad 2/3 levels in the presence of Ang II. Cardiac fibroblasts with and without testosterone had similar mRNA and protein expressions of total Akt and total Smad 2/3 irrespective of TGF-β1 or Ang II treatment. Conclusion: Physiological level of testosterone attenuated Akt and Smad 2/3 phosphorylation mediated by TGF- β1 and angiotensin II respectively, which can result in decreased cardiac fibroblast activation and potentially contribute to beneficial effects in heart failure.

Original languageEnglish
Pages (from-to)386-393
Number of pages8
JournalInternational Journal of Cardiology
Volume176
Issue number2
DOIs
Publication statusPublished - 2014

Fingerprint

Transforming Growth Factors
Angiotensin II
Androgens
Testosterone
Fibroblasts
Collagen
Myofibroblasts
Heart Failure
Tacrolimus Binding Proteins
Matrix Metalloproteinase 2
Fluorescence Microscopy
Cell Movement
Fibrosis
Western Blotting
Phosphorylation
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Angiotensin
  • Fibroblasts
  • Heart failure
  • Testosterone
  • Transforming growth factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

@article{19b2ff07429e4965bf262842905cac94,
title = "Androgen attenuates cardiac fibroblasts activations throughmodulations of transforming growth factor-β and angiotensin II signaling",
abstract = "Background: Androgen deficiency produces heart failure, which can be ameliorated by testosterone supplementation. Cardiac fibrosis plays a critical role in the pathophysiology of heart failure. This study aimed to evaluate whether testosterone can attenuate cardiac fibroblast activity through modulating transforming growth factor (TGF)-β and angiotensin (Ang) II signaling. Methods:Migration, proliferation, myofibroblast differentiation, collagen production, and transcription signaling were evaluated in adult male rat (weighing 300-350 g) cardiac fibroblasts with and without incubation with testosterone (10 nM) and co-administration of TGF-β1 (10 ng/ml) or Ang II (100 nM) by cell migration analysis, proliferation assay, soluble collagenmeasurement, zymographic analysis, immunofluorescence microscopy, realtime PCR and Western blot. Results: Compared to thosewithout testosterone, testosterone-treated fibroblasts exhibited less collagen production. Testosterone-treated fibroblasts also had less migration, proliferation, myofibroblast differentiation, and collagen production in the presence of TGF-β1, or had less collagen production with Ang II. Testosteronetreated fibroblasts had decreased phosphorylated Akt, mammalian target of rapamycin, and 4E binding protein-1 irrespective of TGF-β1 treatment and had increased matrix metalloproteinase (MMP)-2 in the presence of TGF-β1 treatment, and had decreased phosphorylated P38 and Smad 2/3 levels in the presence of Ang II. Cardiac fibroblasts with and without testosterone had similar mRNA and protein expressions of total Akt and total Smad 2/3 irrespective of TGF-β1 or Ang II treatment. Conclusion: Physiological level of testosterone attenuated Akt and Smad 2/3 phosphorylation mediated by TGF- β1 and angiotensin II respectively, which can result in decreased cardiac fibroblast activation and potentially contribute to beneficial effects in heart failure.",
keywords = "Angiotensin, Fibroblasts, Heart failure, Testosterone, Transforming growth factor",
author = "Chung, {Cheng Chih} and Hsu, {Rung Chieh} and Kao, {Yu Hsun} and Liou, {Jing Ping} and Lu, {Yen Yu} and Chen, {Yi Jen}",
year = "2014",
doi = "10.1016/j.ijcard.2014.07.077",
language = "English",
volume = "176",
pages = "386--393",
journal = "International Journal of Cardiology",
issn = "0167-5273",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - Androgen attenuates cardiac fibroblasts activations throughmodulations of transforming growth factor-β and angiotensin II signaling

AU - Chung, Cheng Chih

AU - Hsu, Rung Chieh

AU - Kao, Yu Hsun

AU - Liou, Jing Ping

AU - Lu, Yen Yu

AU - Chen, Yi Jen

PY - 2014

Y1 - 2014

N2 - Background: Androgen deficiency produces heart failure, which can be ameliorated by testosterone supplementation. Cardiac fibrosis plays a critical role in the pathophysiology of heart failure. This study aimed to evaluate whether testosterone can attenuate cardiac fibroblast activity through modulating transforming growth factor (TGF)-β and angiotensin (Ang) II signaling. Methods:Migration, proliferation, myofibroblast differentiation, collagen production, and transcription signaling were evaluated in adult male rat (weighing 300-350 g) cardiac fibroblasts with and without incubation with testosterone (10 nM) and co-administration of TGF-β1 (10 ng/ml) or Ang II (100 nM) by cell migration analysis, proliferation assay, soluble collagenmeasurement, zymographic analysis, immunofluorescence microscopy, realtime PCR and Western blot. Results: Compared to thosewithout testosterone, testosterone-treated fibroblasts exhibited less collagen production. Testosterone-treated fibroblasts also had less migration, proliferation, myofibroblast differentiation, and collagen production in the presence of TGF-β1, or had less collagen production with Ang II. Testosteronetreated fibroblasts had decreased phosphorylated Akt, mammalian target of rapamycin, and 4E binding protein-1 irrespective of TGF-β1 treatment and had increased matrix metalloproteinase (MMP)-2 in the presence of TGF-β1 treatment, and had decreased phosphorylated P38 and Smad 2/3 levels in the presence of Ang II. Cardiac fibroblasts with and without testosterone had similar mRNA and protein expressions of total Akt and total Smad 2/3 irrespective of TGF-β1 or Ang II treatment. Conclusion: Physiological level of testosterone attenuated Akt and Smad 2/3 phosphorylation mediated by TGF- β1 and angiotensin II respectively, which can result in decreased cardiac fibroblast activation and potentially contribute to beneficial effects in heart failure.

AB - Background: Androgen deficiency produces heart failure, which can be ameliorated by testosterone supplementation. Cardiac fibrosis plays a critical role in the pathophysiology of heart failure. This study aimed to evaluate whether testosterone can attenuate cardiac fibroblast activity through modulating transforming growth factor (TGF)-β and angiotensin (Ang) II signaling. Methods:Migration, proliferation, myofibroblast differentiation, collagen production, and transcription signaling were evaluated in adult male rat (weighing 300-350 g) cardiac fibroblasts with and without incubation with testosterone (10 nM) and co-administration of TGF-β1 (10 ng/ml) or Ang II (100 nM) by cell migration analysis, proliferation assay, soluble collagenmeasurement, zymographic analysis, immunofluorescence microscopy, realtime PCR and Western blot. Results: Compared to thosewithout testosterone, testosterone-treated fibroblasts exhibited less collagen production. Testosterone-treated fibroblasts also had less migration, proliferation, myofibroblast differentiation, and collagen production in the presence of TGF-β1, or had less collagen production with Ang II. Testosteronetreated fibroblasts had decreased phosphorylated Akt, mammalian target of rapamycin, and 4E binding protein-1 irrespective of TGF-β1 treatment and had increased matrix metalloproteinase (MMP)-2 in the presence of TGF-β1 treatment, and had decreased phosphorylated P38 and Smad 2/3 levels in the presence of Ang II. Cardiac fibroblasts with and without testosterone had similar mRNA and protein expressions of total Akt and total Smad 2/3 irrespective of TGF-β1 or Ang II treatment. Conclusion: Physiological level of testosterone attenuated Akt and Smad 2/3 phosphorylation mediated by TGF- β1 and angiotensin II respectively, which can result in decreased cardiac fibroblast activation and potentially contribute to beneficial effects in heart failure.

KW - Angiotensin

KW - Fibroblasts

KW - Heart failure

KW - Testosterone

KW - Transforming growth factor

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U2 - 10.1016/j.ijcard.2014.07.077

DO - 10.1016/j.ijcard.2014.07.077

M3 - Article

VL - 176

SP - 386

EP - 393

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

IS - 2

ER -