Skip Navigation


Cardiovascular Research Advance Access first published online on August 20, 2008
This version [Corrected Proof] published online on September 15, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn231
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
81/1/140    most recent
cvn231v2
cvn231v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Liu, Y.
Right arrow Articles by Liang, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, Y.
Right arrow Articles by Liang, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Glucocorticoid response elements and 11β-hydroxysteroid dehydrogenases in the regulation of endothelial nitric oxide synthase expression

Yong Liu{dagger}, Domagoj Mladinov{dagger}, Jennifer L. Pietrusz, Kristie Usa and Mingyu Liang*

Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA

* Corresponding author. Tel: +1 414 456 8539; fax: +1 414 456 6546. E-mail address: mliang{at}mcw.edu

Aims: Hypertensive and other effects of excess glucocorticoids might be in part mediated by the suppression of endothelial nitric oxide synthase (eNOS) expression. We studied the transcriptional and biochemical mechanisms that mediate or modulate the suppression of eNOS expression by glucocorticoids.

Methods and results: We found that a mere three-fold increase in the concentration of the natural glucocorticoid cortisol (from 30 to 100 nmol/L) significantly decreased the expression level of eNOS in human endothelial cells. Deletion analysis of the eNOS promoter indicated that the segment within –119 bp upstream from the transcription start site was significantly involved in the effect of cortisol. Site-directed mutagenesis and chromatin immunoprecipitation analyses demonstrated the presence of a suppressive glucocorticoid response element (GRE) at –111 to –105 bp. 11β-hydroxysteroid dehydrogenases (11β-HSD) catalyse the interconversion of active and inactive glucocorticoids. The suppression of 11β-HSD2 using small interfering RNA markedly exacerbated the inhibition of eNOS by cortisol. The suppression of 11β-HSD1 abolished the inhibition of eNOS expression by cortisol.

Conclusion: We identified the first GRE in the eNOS promoter region and demonstrated that endogenous 11β-HSD1 and 11β-HSD2 play significant and distinct roles in modulating the effect of glucocorticoids on eNOS expression.

KEYWORDS Hypertension; Promoter; Gene expression; Endothelium; RNA interference

Time for primary review: 20 days

{dagger} The first two authors contributed equally to this work.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 HypertensionHome page
Z. Tian, Y. Liu, K. Usa, D. Mladinov, Y. Fang, X. Ding, A. S. Greene, A. W. Cowley Jr, and M. Liang
Novel Role of Fumarate Metabolism in Dahl-Salt Sensitive Hypertension
Hypertension, August 1, 2009; 54(2): 255 - 260.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.