Mechanism of the inhibitory effect of atorvastatin on endoglin expression induced by transforming growth factor-1 in cultured cardiac fibroblasts

Kou Gi Shyu, Bao Wei Wang, Wei Jan Chen, Peiliang Kuan, Chi Ren Hung

研究成果: 雜誌貢獻文章

35 引文 (Scopus)

摘要

AimsTransforming growth factor-1 (TGF-1) and endoglin play a causal role in promoting cardiac fibrosis. Atorvastatin has been shown to have an inhibitory effect on cardiac fibroblasts in vitro. However, the effects of statins on TGF-1 and endoglin are poorly understood. We therefore sought to investigate the molecular mechanisms of atorvastatin on endoglin expression after TGF-1 stimulation in cardiac fibroblasts.Methods and resultsCultured cardiac fibroblasts were obtained from adult male Sprague-Dawley rat hearts. TGF-1 stimulation increased endoglin and collagen I expression and atorvastatin inhibited the induction of endoglin and collagen I by TGF-1. Phosphatidylinositol-3 kinase (PI-3) and Akt inhibitors (wortmannin and Akt inhibitor X) completely attenuated the endoglin protein expression induced by TGF-1. TGF-1 induced phosphorylation of PI-3 kinase and Akt, while atorvastatin and wortmannin and Akt inhibitor X inhibited the phosphorylation of PI-3 kinase and Akt induced by TGF-1. The gel shift and promoter activity assay showed that TGF-1 increased Smad3/4-binding activity and endoglin promoter activity, while wortmannin and atorvastatin inhibited the Smad3/4-binding activity and endoglin promoter activity induced by TGF-1. TGF-1 increased collagen I protein expression, while endoglin siRNA attenuated collagen I protein expression induced by TGF-1. Atorvastatin decreased left ventricular TGF-1, endoglin, and collagen I protein expression and fibrotic area in a rat model of volume overload heart failure.ConclusionAtorvastatin inhibits endoglin expression through the inhibition of PI-3 kinase, Akt, and Smad3 phosphorylation, and reduced Smad3/4 binding activity and endoglin promoter activity in cardiac fibroblasts.
原文英語
頁(從 - 到)219-226
頁數8
期刊European Journal of Heart Failure
12
發行號3
DOIs
出版狀態已發佈 - 三月 2010

指紋

Transforming Growth Factors
Fibroblasts
Phosphatidylinositol 3-Kinase
Collagen
Phosphotransferases
Phosphorylation
Atorvastatin Calcium
Endoglin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Proteins
Small Interfering RNA
Sprague Dawley Rats
Intercellular Signaling Peptides and Proteins
Fibrosis
Heart Failure
Gels

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

引用此文

Mechanism of the inhibitory effect of atorvastatin on endoglin expression induced by transforming growth factor-1 in cultured cardiac fibroblasts. / Shyu, Kou Gi; Wang, Bao Wei; Chen, Wei Jan; Kuan, Peiliang; Hung, Chi Ren.

於: European Journal of Heart Failure, 卷 12, 編號 3, 03.2010, p. 219-226.

研究成果: 雜誌貢獻文章

Shyu, Kou Gi ; Wang, Bao Wei ; Chen, Wei Jan ; Kuan, Peiliang ; Hung, Chi Ren. / Mechanism of the inhibitory effect of atorvastatin on endoglin expression induced by transforming growth factor-1 in cultured cardiac fibroblasts. 於: European Journal of Heart Failure. 2010 ; 卷 12, 編號 3. 頁 219-226.
@article{40b7ceec83384ef3af3a8a4af32fad55,
title = "Mechanism of the inhibitory effect of atorvastatin on endoglin expression induced by transforming growth factor-1 in cultured cardiac fibroblasts",
abstract = "AimsTransforming growth factor-1 (TGF-1) and endoglin play a causal role in promoting cardiac fibrosis. Atorvastatin has been shown to have an inhibitory effect on cardiac fibroblasts in vitro. However, the effects of statins on TGF-1 and endoglin are poorly understood. We therefore sought to investigate the molecular mechanisms of atorvastatin on endoglin expression after TGF-1 stimulation in cardiac fibroblasts.Methods and resultsCultured cardiac fibroblasts were obtained from adult male Sprague-Dawley rat hearts. TGF-1 stimulation increased endoglin and collagen I expression and atorvastatin inhibited the induction of endoglin and collagen I by TGF-1. Phosphatidylinositol-3 kinase (PI-3) and Akt inhibitors (wortmannin and Akt inhibitor X) completely attenuated the endoglin protein expression induced by TGF-1. TGF-1 induced phosphorylation of PI-3 kinase and Akt, while atorvastatin and wortmannin and Akt inhibitor X inhibited the phosphorylation of PI-3 kinase and Akt induced by TGF-1. The gel shift and promoter activity assay showed that TGF-1 increased Smad3/4-binding activity and endoglin promoter activity, while wortmannin and atorvastatin inhibited the Smad3/4-binding activity and endoglin promoter activity induced by TGF-1. TGF-1 increased collagen I protein expression, while endoglin siRNA attenuated collagen I protein expression induced by TGF-1. Atorvastatin decreased left ventricular TGF-1, endoglin, and collagen I protein expression and fibrotic area in a rat model of volume overload heart failure.ConclusionAtorvastatin inhibits endoglin expression through the inhibition of PI-3 kinase, Akt, and Smad3 phosphorylation, and reduced Smad3/4 binding activity and endoglin promoter activity in cardiac fibroblasts.",
keywords = "Endoglin, Fibroblast, Fibrosis, Statin, Transforming growth factor-β1",
author = "Shyu, {Kou Gi} and Wang, {Bao Wei} and Chen, {Wei Jan} and Peiliang Kuan and Hung, {Chi Ren}",
year = "2010",
month = "3",
doi = "10.1093/eurjhf/hfq011",
language = "English",
volume = "12",
pages = "219--226",
journal = "European Journal of Heart Failure",
issn = "1388-9842",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Mechanism of the inhibitory effect of atorvastatin on endoglin expression induced by transforming growth factor-1 in cultured cardiac fibroblasts

AU - Shyu, Kou Gi

AU - Wang, Bao Wei

AU - Chen, Wei Jan

AU - Kuan, Peiliang

AU - Hung, Chi Ren

PY - 2010/3

Y1 - 2010/3

N2 - AimsTransforming growth factor-1 (TGF-1) and endoglin play a causal role in promoting cardiac fibrosis. Atorvastatin has been shown to have an inhibitory effect on cardiac fibroblasts in vitro. However, the effects of statins on TGF-1 and endoglin are poorly understood. We therefore sought to investigate the molecular mechanisms of atorvastatin on endoglin expression after TGF-1 stimulation in cardiac fibroblasts.Methods and resultsCultured cardiac fibroblasts were obtained from adult male Sprague-Dawley rat hearts. TGF-1 stimulation increased endoglin and collagen I expression and atorvastatin inhibited the induction of endoglin and collagen I by TGF-1. Phosphatidylinositol-3 kinase (PI-3) and Akt inhibitors (wortmannin and Akt inhibitor X) completely attenuated the endoglin protein expression induced by TGF-1. TGF-1 induced phosphorylation of PI-3 kinase and Akt, while atorvastatin and wortmannin and Akt inhibitor X inhibited the phosphorylation of PI-3 kinase and Akt induced by TGF-1. The gel shift and promoter activity assay showed that TGF-1 increased Smad3/4-binding activity and endoglin promoter activity, while wortmannin and atorvastatin inhibited the Smad3/4-binding activity and endoglin promoter activity induced by TGF-1. TGF-1 increased collagen I protein expression, while endoglin siRNA attenuated collagen I protein expression induced by TGF-1. Atorvastatin decreased left ventricular TGF-1, endoglin, and collagen I protein expression and fibrotic area in a rat model of volume overload heart failure.ConclusionAtorvastatin inhibits endoglin expression through the inhibition of PI-3 kinase, Akt, and Smad3 phosphorylation, and reduced Smad3/4 binding activity and endoglin promoter activity in cardiac fibroblasts.

AB - AimsTransforming growth factor-1 (TGF-1) and endoglin play a causal role in promoting cardiac fibrosis. Atorvastatin has been shown to have an inhibitory effect on cardiac fibroblasts in vitro. However, the effects of statins on TGF-1 and endoglin are poorly understood. We therefore sought to investigate the molecular mechanisms of atorvastatin on endoglin expression after TGF-1 stimulation in cardiac fibroblasts.Methods and resultsCultured cardiac fibroblasts were obtained from adult male Sprague-Dawley rat hearts. TGF-1 stimulation increased endoglin and collagen I expression and atorvastatin inhibited the induction of endoglin and collagen I by TGF-1. Phosphatidylinositol-3 kinase (PI-3) and Akt inhibitors (wortmannin and Akt inhibitor X) completely attenuated the endoglin protein expression induced by TGF-1. TGF-1 induced phosphorylation of PI-3 kinase and Akt, while atorvastatin and wortmannin and Akt inhibitor X inhibited the phosphorylation of PI-3 kinase and Akt induced by TGF-1. The gel shift and promoter activity assay showed that TGF-1 increased Smad3/4-binding activity and endoglin promoter activity, while wortmannin and atorvastatin inhibited the Smad3/4-binding activity and endoglin promoter activity induced by TGF-1. TGF-1 increased collagen I protein expression, while endoglin siRNA attenuated collagen I protein expression induced by TGF-1. Atorvastatin decreased left ventricular TGF-1, endoglin, and collagen I protein expression and fibrotic area in a rat model of volume overload heart failure.ConclusionAtorvastatin inhibits endoglin expression through the inhibition of PI-3 kinase, Akt, and Smad3 phosphorylation, and reduced Smad3/4 binding activity and endoglin promoter activity in cardiac fibroblasts.

KW - Endoglin

KW - Fibroblast

KW - Fibrosis

KW - Statin

KW - Transforming growth factor-β1

UR - http://www.scopus.com/inward/record.url?scp=77249121584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77249121584&partnerID=8YFLogxK

U2 - 10.1093/eurjhf/hfq011

DO - 10.1093/eurjhf/hfq011

M3 - Article

C2 - 20156938

AN - SCOPUS:77249121584

VL - 12

SP - 219

EP - 226

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

SN - 1388-9842

IS - 3

ER -