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This Article Full Text Full Text (PDF) All Versions of this Article: 287/3/H1254    most recent 00723.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (22) Citing Articles via Google Scholar Google Scholar Articles by Juan, S.-H. Articles by Cheng, T.-H. Search for Related Content PubMed PubMed Citation Articles by Juan, S.-H. Articles by Cheng, T.-H.

17-Estradiol inhibits cyclic strain-induced endothelin-1 gene expression within vascular endothelial cells

¹Graduate Institute of Medical Sciences and Department of Physiology, School of Medicine; ²Department of Medicine, Taipei Medical University, Taipei 100; ³Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 110; ⁴Institute of Biomedical Sciences, Academia Sinica, Taipei 115; ⁵Department of Medicine and Clinical Research Center, Taipei Medical University-Wan Fang Hospital, Taipei 117; and ⁶Department of Cardiovascular Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan, Republic of China

Submitted 28 July 2003 ; accepted in final form 4 May 2004

It has been well documented previously that 17-estradiol (E₂) exerts a protective effect on cardiovascular tissue. The possible role of E₂ in the regulation of endothelin (ET)-1 production has been previously reported, although the complex mechanisms by which E₂ inhibits ET-1 expression are not completely understood. The aims of this study were to examine whether E₂ was able to alter strain-induced ET-1 gene expression and also to identify the putative underlying signaling pathways that exist within endothelial cells. For cultured endothelial cells, E₂ (1–100 nM), but not 17-estradiol, inhibited the level of strain-induced ET-1 gene expression and also peptide secretion. This inhibitory effect elicited by E₂ was able to be prevented by the coincubation of endothelial cells with the estrogen receptor antagonist ICI-182,780 (1 µM). E₂ also inhibited strain-enhanced NADPH oxidase activity and intracellular reactive oxygen species (ROS) generation as measured by the redox-sensitive fluorescent dye 2',7'-dichlorofluorescin diacetate and the level of extracellular signal-regulated kinase (ERK) phosphorylation. Furthermore, the presence of E₂ and antioxidants such as N-acetylcysteine and diphenylene iodonium were able to elicit a decrease in the level of strain-induced ET-1 secretion, ET-1 promoter activity, ET-1 mRNA, ERK phosphorylation, and activator protein-1 binding activity. In summary, we demonstrated, for the first time, that E₂ inhibits strain-induced ET-1 gene expression, partially by interfering with the ERK pathway via the attenuation of strain-induced ROS generation. Thus this study delivers important new insight regarding the molecular pathways that may contribute to the proposed beneficial effects of estrogen on the cardiovascular system.

strain; reactive oxygen species; extracellular signal-regulated kinase

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