Oxidative stress mediates cardiac fibrosis by enhancing transforming growth factor-beta1 in hypertensive rats

Wenyuan Zhao, Tieqiang Zhao, Yuanjian Chen, Robert A. Ahokas, Yao Sun

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Cardiac fibrosis represented as perivascular/interstial fibrosis occurs in patients with hypertension. Oxidative stress has been demonstrated to contribute to such structural remodeling. The underlying mechanisms, however, remain to be elucidated. Herein, we tested the hypothesis that oxidative stress mediates cardiac fibrogenesis by stimulating transforming growth factor (TGF)-β1 expression, which in turn triggers a series of fibrogenic responses. Sprague - Dawley rats were treated with angiotensin (Ang)II (9 μg/h s) for 4 weeks with/without co-treatment of combined antioxidants, apocynin, and tempol (120 mg/kg/ day each, oral). Untreated rats served as controls. Appearance of cardiac oxidative stress and its potential effect on the expression of TGF-β1, population of myofibroblasts, collagen synthesis/ degradation, and fibrosis in hearts were examined. Chronic AngII infusion elevated systemic blood pressure (210 ± 5 mmHg). Extensive perivascular and interstitial fibrosis was found in both ventricles, which were co-localized with oxidative stress represented as upregulated NADPH oxidase (gp91phox subunit) expression. Co-treatment with antioxidants led to: (1) markedly decreased cardiac gp91phox; (2) significantly attenuated gene expression of TGF-β1, type-I collagen, and tissue inhibitors of matrix metalloproteinase (TIMP)-I/II in the heart; (3) largely reduced population of myofibroblasts at sites of fibrosis; (4) significantly reduced cardiac collagen volume; (5) and partially suppressed blood pressure (190 ± 4 mmHg). Thus, cardiac oxidative stress promotes the development of cardiac fibrosis by upregulating TGF-β1 expression, which subsequently enhances cardiac collagen synthesis and suppresses collagen degradation in hypertensive rats.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume317
Issue number1-2
DOIs
StatePublished - Jun 26 2008

Fingerprint

Transforming Growth Factor beta1
Oxidative stress
Rats
Transforming Growth Factors
Oxidative Stress
Fibrosis
Collagen
Blood pressure
Myofibroblasts
Antioxidants
Degradation
Matrix Metalloproteinase Inhibitors
NADPH Oxidase
Blood Pressure
Tissue Inhibitor of Metalloproteinases
Cardiac Volume
Collagen Type I
Gene expression
Angiotensin II
Population

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Oxidative stress mediates cardiac fibrosis by enhancing transforming growth factor-beta1 in hypertensive rats. / Zhao, Wenyuan; Zhao, Tieqiang; Chen, Yuanjian; Ahokas, Robert A.; Sun, Yao.

In: Molecular and Cellular Biochemistry, Vol. 317, No. 1-2, 26.06.2008, p. 43-50.

Research output: Contribution to journalArticle

Zhao, Wenyuan ; Zhao, Tieqiang ; Chen, Yuanjian ; Ahokas, Robert A. ; Sun, Yao. / Oxidative stress mediates cardiac fibrosis by enhancing transforming growth factor-beta1 in hypertensive rats. In: Molecular and Cellular Biochemistry. 2008 ; Vol. 317, No. 1-2. pp. 43-50.
@article{467322c39e0043f2a3005f105cddb12e,
title = "Oxidative stress mediates cardiac fibrosis by enhancing transforming growth factor-beta1 in hypertensive rats",
abstract = "Cardiac fibrosis represented as perivascular/interstial fibrosis occurs in patients with hypertension. Oxidative stress has been demonstrated to contribute to such structural remodeling. The underlying mechanisms, however, remain to be elucidated. Herein, we tested the hypothesis that oxidative stress mediates cardiac fibrogenesis by stimulating transforming growth factor (TGF)-β1 expression, which in turn triggers a series of fibrogenic responses. Sprague - Dawley rats were treated with angiotensin (Ang)II (9 μg/h s) for 4 weeks with/without co-treatment of combined antioxidants, apocynin, and tempol (120 mg/kg/ day each, oral). Untreated rats served as controls. Appearance of cardiac oxidative stress and its potential effect on the expression of TGF-β1, population of myofibroblasts, collagen synthesis/ degradation, and fibrosis in hearts were examined. Chronic AngII infusion elevated systemic blood pressure (210 ± 5 mmHg). Extensive perivascular and interstitial fibrosis was found in both ventricles, which were co-localized with oxidative stress represented as upregulated NADPH oxidase (gp91phox subunit) expression. Co-treatment with antioxidants led to: (1) markedly decreased cardiac gp91phox; (2) significantly attenuated gene expression of TGF-β1, type-I collagen, and tissue inhibitors of matrix metalloproteinase (TIMP)-I/II in the heart; (3) largely reduced population of myofibroblasts at sites of fibrosis; (4) significantly reduced cardiac collagen volume; (5) and partially suppressed blood pressure (190 ± 4 mmHg). Thus, cardiac oxidative stress promotes the development of cardiac fibrosis by upregulating TGF-β1 expression, which subsequently enhances cardiac collagen synthesis and suppresses collagen degradation in hypertensive rats.",
author = "Wenyuan Zhao and Tieqiang Zhao and Yuanjian Chen and Ahokas, {Robert A.} and Yao Sun",
year = "2008",
month = "6",
day = "26",
doi = "10.1007/s11010-008-9803-8",
language = "English (US)",
volume = "317",
pages = "43--50",
journal = "Molecular and Cellular Biochemistry",
issn = "0300-8177",
publisher = "Springer Netherlands",
number = "1-2",

}

TY - JOUR

T1 - Oxidative stress mediates cardiac fibrosis by enhancing transforming growth factor-beta1 in hypertensive rats

AU - Zhao, Wenyuan

AU - Zhao, Tieqiang

AU - Chen, Yuanjian

AU - Ahokas, Robert A.

AU - Sun, Yao

PY - 2008/6/26

Y1 - 2008/6/26

N2 - Cardiac fibrosis represented as perivascular/interstial fibrosis occurs in patients with hypertension. Oxidative stress has been demonstrated to contribute to such structural remodeling. The underlying mechanisms, however, remain to be elucidated. Herein, we tested the hypothesis that oxidative stress mediates cardiac fibrogenesis by stimulating transforming growth factor (TGF)-β1 expression, which in turn triggers a series of fibrogenic responses. Sprague - Dawley rats were treated with angiotensin (Ang)II (9 μg/h s) for 4 weeks with/without co-treatment of combined antioxidants, apocynin, and tempol (120 mg/kg/ day each, oral). Untreated rats served as controls. Appearance of cardiac oxidative stress and its potential effect on the expression of TGF-β1, population of myofibroblasts, collagen synthesis/ degradation, and fibrosis in hearts were examined. Chronic AngII infusion elevated systemic blood pressure (210 ± 5 mmHg). Extensive perivascular and interstitial fibrosis was found in both ventricles, which were co-localized with oxidative stress represented as upregulated NADPH oxidase (gp91phox subunit) expression. Co-treatment with antioxidants led to: (1) markedly decreased cardiac gp91phox; (2) significantly attenuated gene expression of TGF-β1, type-I collagen, and tissue inhibitors of matrix metalloproteinase (TIMP)-I/II in the heart; (3) largely reduced population of myofibroblasts at sites of fibrosis; (4) significantly reduced cardiac collagen volume; (5) and partially suppressed blood pressure (190 ± 4 mmHg). Thus, cardiac oxidative stress promotes the development of cardiac fibrosis by upregulating TGF-β1 expression, which subsequently enhances cardiac collagen synthesis and suppresses collagen degradation in hypertensive rats.

AB - Cardiac fibrosis represented as perivascular/interstial fibrosis occurs in patients with hypertension. Oxidative stress has been demonstrated to contribute to such structural remodeling. The underlying mechanisms, however, remain to be elucidated. Herein, we tested the hypothesis that oxidative stress mediates cardiac fibrogenesis by stimulating transforming growth factor (TGF)-β1 expression, which in turn triggers a series of fibrogenic responses. Sprague - Dawley rats were treated with angiotensin (Ang)II (9 μg/h s) for 4 weeks with/without co-treatment of combined antioxidants, apocynin, and tempol (120 mg/kg/ day each, oral). Untreated rats served as controls. Appearance of cardiac oxidative stress and its potential effect on the expression of TGF-β1, population of myofibroblasts, collagen synthesis/ degradation, and fibrosis in hearts were examined. Chronic AngII infusion elevated systemic blood pressure (210 ± 5 mmHg). Extensive perivascular and interstitial fibrosis was found in both ventricles, which were co-localized with oxidative stress represented as upregulated NADPH oxidase (gp91phox subunit) expression. Co-treatment with antioxidants led to: (1) markedly decreased cardiac gp91phox; (2) significantly attenuated gene expression of TGF-β1, type-I collagen, and tissue inhibitors of matrix metalloproteinase (TIMP)-I/II in the heart; (3) largely reduced population of myofibroblasts at sites of fibrosis; (4) significantly reduced cardiac collagen volume; (5) and partially suppressed blood pressure (190 ± 4 mmHg). Thus, cardiac oxidative stress promotes the development of cardiac fibrosis by upregulating TGF-β1 expression, which subsequently enhances cardiac collagen synthesis and suppresses collagen degradation in hypertensive rats.

UR - http://www.scopus.com/inward/record.url?scp=53149102406&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53149102406&partnerID=8YFLogxK

U2 - 10.1007/s11010-008-9803-8

DO - 10.1007/s11010-008-9803-8

M3 - Article

VL - 317

SP - 43

EP - 50

JO - Molecular and Cellular Biochemistry

JF - Molecular and Cellular Biochemistry

SN - 0300-8177

IS - 1-2

ER -