Abstract

Background: The association between hyperuricemia and cardiovascular diseases has long been recognized. Elevated levels of uric acid may have a causal role in hypertension and cardiovascular diseases. However, the direct effect of uric acid on cardiac cells remains unclear. Therefore, this study was aimed to examine the effect of uric acid in rat cardiac fibroblasts and to identify the putative underlying signaling pathways. Methods: Cultured rat cardiac fibroblasts were stimulated with uric acid; cell proliferation and endothelin-1 (ET-1) gene expression were examined. The effect of uric acid on NADPH oxidase activity, reactive oxygen species (ROS) formation, and extracellular signal-regulated kinases (ERK) phosphorylation were tested to elucidate the intracellular mechanism of uric acid in ET-1 gene expression. Results: Uric acid-increased cell proliferation and ET-1 gene expression. Uric acid also increased NADPH oxidase activity, ROS formation, ERK phosphorylation, and activator protein-1 (AP-1)-mediated reporter activity. Antioxidants suppressed uric acid-induced ET-1 gene expression, and ERK phosphorylation, and AP-1 reporter activities. Mutational analysis of the ET-1 gene promoter showed that AP-1 binding site was an important cis-element in uric acid-induced ET-1 gene expression. Conclusions: These results suggest that uric acid-induced ET-1 gene expression, partially by the activation of ERK pathway via ROS generation in cardiac fibroblasts.

Original languageEnglish
Pages (from-to)42-49
Number of pages8
JournalInternational Journal of Cardiology
Volume139
Issue number1
DOIs
Publication statusPublished - Feb 18 2010

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Extracellular Signal-Regulated MAP Kinases
Endothelin-1
Uric Acid
Fibroblasts
Gene Expression
Transcription Factor AP-1
Reactive Oxygen Species
NADPH Oxidase
Phosphorylation
Cardiovascular Diseases
Cell Proliferation
Hyperuricemia
Protein Binding
Antioxidants
Binding Sites
Hypertension

Keywords

  • Cardiac fibroblasts
  • Endothelin-1
  • Extracellular signal-regulated kinases
  • Reactive oxygen species
  • Uric acid

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Uric acid activates extracellular signal-regulated kinases and thereafter endothelin-1 expression in rat cardiac fibroblasts. / Cheng, Tzu-Hurng; Lin, Jia Wei; Chao, Hung Hsin; Chen, Yen Ling; Chen, Cheng Hsien; Chan, Paul; Liu, Ju Chi.

In: International Journal of Cardiology, Vol. 139, No. 1, 18.02.2010, p. 42-49.

Research output: Contribution to journalArticle

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abstract = "Background: The association between hyperuricemia and cardiovascular diseases has long been recognized. Elevated levels of uric acid may have a causal role in hypertension and cardiovascular diseases. However, the direct effect of uric acid on cardiac cells remains unclear. Therefore, this study was aimed to examine the effect of uric acid in rat cardiac fibroblasts and to identify the putative underlying signaling pathways. Methods: Cultured rat cardiac fibroblasts were stimulated with uric acid; cell proliferation and endothelin-1 (ET-1) gene expression were examined. The effect of uric acid on NADPH oxidase activity, reactive oxygen species (ROS) formation, and extracellular signal-regulated kinases (ERK) phosphorylation were tested to elucidate the intracellular mechanism of uric acid in ET-1 gene expression. Results: Uric acid-increased cell proliferation and ET-1 gene expression. Uric acid also increased NADPH oxidase activity, ROS formation, ERK phosphorylation, and activator protein-1 (AP-1)-mediated reporter activity. Antioxidants suppressed uric acid-induced ET-1 gene expression, and ERK phosphorylation, and AP-1 reporter activities. Mutational analysis of the ET-1 gene promoter showed that AP-1 binding site was an important cis-element in uric acid-induced ET-1 gene expression. Conclusions: These results suggest that uric acid-induced ET-1 gene expression, partially by the activation of ERK pathway via ROS generation in cardiac fibroblasts.",
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author = "Tzu-Hurng Cheng and Lin, {Jia Wei} and Chao, {Hung Hsin} and Chen, {Yen Ling} and Chen, {Cheng Hsien} and Paul Chan and Liu, {Ju Chi}",
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AU - Cheng, Tzu-Hurng

AU - Lin, Jia Wei

AU - Chao, Hung Hsin

AU - Chen, Yen Ling

AU - Chen, Cheng Hsien

AU - Chan, Paul

AU - Liu, Ju Chi

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