Attenuation of cardiac dysfunction by a PPAR-α agonist is associated with down-regulation of redox-regulated transcription factors

Sahoko Ichihara, Koji Obata, Yoshiji Yamada, Kohzo Nagata, Akiko Noda, Gaku Ichihara, Akira Yamada, Tomoko Kato, Hideo Izawa, Toyoaki Murohara, Mitsuhiro Yokota

研究成果: Article

89 引用 (Scopus)

抄録

Peroxisome proliferator-activated receptor-α (PPAR-α) is a key regulator of lipid and glucose metabolism and is implicated in inflammation. We investigated the effects of the PPAR-α activator fenofibrate on, as well as the role of redox-regulated transcription factors, in the development of left ventricular (LV) hypertrophy and heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed a high-salt diet and treated with either fenofibrate (30 or 50 mg/kg per day) or vehicle from 7 weeks of age. Fenofibrate inhibited the development of compensated hypertensive LV hypertrophy, attenuated the LV relaxation abnormality and systolic dysfunction, and improved the survival rate in DS rats. It also prevented a decrease in the ratio of reduced to oxidized glutathione and inhibited up-regulation of the DNA binding activities of the redox-regulated transcription factors NF-κB, AP-1, Egr-1, SP1, and Ets-1 induced in the left ventricle by the high-salt diet. Expression of target genes for these transcription factors, including those for adhesion molecules (VCAM-1, ICAM-1), cytokines (MCP-1), growth factors (TGF-β, PDGF-B), and osteopontin, was also increased by the high-salt diet in a manner sensitive to treatment with fenofibrate. Furthermore, the infiltration of macrophages and T lymphocytes into the left ventricle and the increase in the plasma concentration of C-reactive protein were inhibited by fenofibrate. The PPAR-α activator fenofibrate thus attenuated the progression of heart failure and improved the survival rate in this rat model. These effects were associated with inhibition of the inflammatory response and of activation of redox-regulated transcription factors in the left ventricle.

元の言語English
ページ(範囲)318-329
ページ数12
ジャーナルJournal of Molecular and Cellular Cardiology
41
発行部数2
DOI
出版物ステータスPublished - 01-08-2006
外部発表Yes

Fingerprint

Fenofibrate
Peroxisome Proliferator-Activated Receptors
Oxidation-Reduction
Transcription Factors
Down-Regulation
Inbred Dahl Rats
Heart Ventricles
Salts
Left Ventricular Hypertrophy
Diet
Heart Failure
Osteopontin
Glutathione Disulfide
Vascular Cell Adhesion Molecule-1
Transcription Factor AP-1
Intercellular Adhesion Molecule-1
Lipid Metabolism
C-Reactive Protein
Intercellular Signaling Peptides and Proteins
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

これを引用

Ichihara, Sahoko ; Obata, Koji ; Yamada, Yoshiji ; Nagata, Kohzo ; Noda, Akiko ; Ichihara, Gaku ; Yamada, Akira ; Kato, Tomoko ; Izawa, Hideo ; Murohara, Toyoaki ; Yokota, Mitsuhiro. / Attenuation of cardiac dysfunction by a PPAR-α agonist is associated with down-regulation of redox-regulated transcription factors. :: Journal of Molecular and Cellular Cardiology. 2006 ; 巻 41, 番号 2. pp. 318-329.
@article{3e28d0093e8b4e6fb37c1833f06b7219,
title = "Attenuation of cardiac dysfunction by a PPAR-α agonist is associated with down-regulation of redox-regulated transcription factors",
abstract = "Peroxisome proliferator-activated receptor-α (PPAR-α) is a key regulator of lipid and glucose metabolism and is implicated in inflammation. We investigated the effects of the PPAR-α activator fenofibrate on, as well as the role of redox-regulated transcription factors, in the development of left ventricular (LV) hypertrophy and heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed a high-salt diet and treated with either fenofibrate (30 or 50 mg/kg per day) or vehicle from 7 weeks of age. Fenofibrate inhibited the development of compensated hypertensive LV hypertrophy, attenuated the LV relaxation abnormality and systolic dysfunction, and improved the survival rate in DS rats. It also prevented a decrease in the ratio of reduced to oxidized glutathione and inhibited up-regulation of the DNA binding activities of the redox-regulated transcription factors NF-κB, AP-1, Egr-1, SP1, and Ets-1 induced in the left ventricle by the high-salt diet. Expression of target genes for these transcription factors, including those for adhesion molecules (VCAM-1, ICAM-1), cytokines (MCP-1), growth factors (TGF-β, PDGF-B), and osteopontin, was also increased by the high-salt diet in a manner sensitive to treatment with fenofibrate. Furthermore, the infiltration of macrophages and T lymphocytes into the left ventricle and the increase in the plasma concentration of C-reactive protein were inhibited by fenofibrate. The PPAR-α activator fenofibrate thus attenuated the progression of heart failure and improved the survival rate in this rat model. These effects were associated with inhibition of the inflammatory response and of activation of redox-regulated transcription factors in the left ventricle.",
author = "Sahoko Ichihara and Koji Obata and Yoshiji Yamada and Kohzo Nagata and Akiko Noda and Gaku Ichihara and Akira Yamada and Tomoko Kato and Hideo Izawa and Toyoaki Murohara and Mitsuhiro Yokota",
year = "2006",
month = "8",
day = "1",
doi = "10.1016/j.yjmcc.2006.05.013",
language = "English",
volume = "41",
pages = "318--329",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "2",

}

Ichihara, S, Obata, K, Yamada, Y, Nagata, K, Noda, A, Ichihara, G, Yamada, A, Kato, T, Izawa, H, Murohara, T & Yokota, M 2006, 'Attenuation of cardiac dysfunction by a PPAR-α agonist is associated with down-regulation of redox-regulated transcription factors', Journal of Molecular and Cellular Cardiology, 巻. 41, 番号 2, pp. 318-329. https://doi.org/10.1016/j.yjmcc.2006.05.013

Attenuation of cardiac dysfunction by a PPAR-α agonist is associated with down-regulation of redox-regulated transcription factors. / Ichihara, Sahoko; Obata, Koji; Yamada, Yoshiji; Nagata, Kohzo; Noda, Akiko; Ichihara, Gaku; Yamada, Akira; Kato, Tomoko; Izawa, Hideo; Murohara, Toyoaki; Yokota, Mitsuhiro.

:: Journal of Molecular and Cellular Cardiology, 巻 41, 番号 2, 01.08.2006, p. 318-329.

研究成果: Article

TY - JOUR

T1 - Attenuation of cardiac dysfunction by a PPAR-α agonist is associated with down-regulation of redox-regulated transcription factors

AU - Ichihara, Sahoko

AU - Obata, Koji

AU - Yamada, Yoshiji

AU - Nagata, Kohzo

AU - Noda, Akiko

AU - Ichihara, Gaku

AU - Yamada, Akira

AU - Kato, Tomoko

AU - Izawa, Hideo

AU - Murohara, Toyoaki

AU - Yokota, Mitsuhiro

PY - 2006/8/1

Y1 - 2006/8/1

N2 - Peroxisome proliferator-activated receptor-α (PPAR-α) is a key regulator of lipid and glucose metabolism and is implicated in inflammation. We investigated the effects of the PPAR-α activator fenofibrate on, as well as the role of redox-regulated transcription factors, in the development of left ventricular (LV) hypertrophy and heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed a high-salt diet and treated with either fenofibrate (30 or 50 mg/kg per day) or vehicle from 7 weeks of age. Fenofibrate inhibited the development of compensated hypertensive LV hypertrophy, attenuated the LV relaxation abnormality and systolic dysfunction, and improved the survival rate in DS rats. It also prevented a decrease in the ratio of reduced to oxidized glutathione and inhibited up-regulation of the DNA binding activities of the redox-regulated transcription factors NF-κB, AP-1, Egr-1, SP1, and Ets-1 induced in the left ventricle by the high-salt diet. Expression of target genes for these transcription factors, including those for adhesion molecules (VCAM-1, ICAM-1), cytokines (MCP-1), growth factors (TGF-β, PDGF-B), and osteopontin, was also increased by the high-salt diet in a manner sensitive to treatment with fenofibrate. Furthermore, the infiltration of macrophages and T lymphocytes into the left ventricle and the increase in the plasma concentration of C-reactive protein were inhibited by fenofibrate. The PPAR-α activator fenofibrate thus attenuated the progression of heart failure and improved the survival rate in this rat model. These effects were associated with inhibition of the inflammatory response and of activation of redox-regulated transcription factors in the left ventricle.

AB - Peroxisome proliferator-activated receptor-α (PPAR-α) is a key regulator of lipid and glucose metabolism and is implicated in inflammation. We investigated the effects of the PPAR-α activator fenofibrate on, as well as the role of redox-regulated transcription factors, in the development of left ventricular (LV) hypertrophy and heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed a high-salt diet and treated with either fenofibrate (30 or 50 mg/kg per day) or vehicle from 7 weeks of age. Fenofibrate inhibited the development of compensated hypertensive LV hypertrophy, attenuated the LV relaxation abnormality and systolic dysfunction, and improved the survival rate in DS rats. It also prevented a decrease in the ratio of reduced to oxidized glutathione and inhibited up-regulation of the DNA binding activities of the redox-regulated transcription factors NF-κB, AP-1, Egr-1, SP1, and Ets-1 induced in the left ventricle by the high-salt diet. Expression of target genes for these transcription factors, including those for adhesion molecules (VCAM-1, ICAM-1), cytokines (MCP-1), growth factors (TGF-β, PDGF-B), and osteopontin, was also increased by the high-salt diet in a manner sensitive to treatment with fenofibrate. Furthermore, the infiltration of macrophages and T lymphocytes into the left ventricle and the increase in the plasma concentration of C-reactive protein were inhibited by fenofibrate. The PPAR-α activator fenofibrate thus attenuated the progression of heart failure and improved the survival rate in this rat model. These effects were associated with inhibition of the inflammatory response and of activation of redox-regulated transcription factors in the left ventricle.

UR - http://www.scopus.com/inward/record.url?scp=33746066382&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746066382&partnerID=8YFLogxK

U2 - 10.1016/j.yjmcc.2006.05.013

DO - 10.1016/j.yjmcc.2006.05.013

M3 - Article

C2 - 16806263

AN - SCOPUS:33746066382

VL - 41

SP - 318

EP - 329

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

SN - 0022-2828

IS - 2

ER -