AJP - Heart AJP: Heart and Circulatory Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol (July 8, 2004). doi:10.1152/ajpheart.00323.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/5/H1977    most recent
00323.2004v1
Right arrow Alert me when this article is cited
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 Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Braam, B.
Right arrow Articles by Koomans, H. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Braam, B.
Right arrow Articles by Koomans, H. A.
Submitted on April 1, 2004
Accepted on June 24, 2004

Nitric Oxide Donor Induces Temporal and Dose-Dependent Reduction of Gene Expression in Human Endothelial Cells

Branko Braam1*, Remmert de Roos1, Adele Dijk1, Peter Boer1, Jan Andries Post2, Patrick PCW Kemmeren3, Frank CP Holstege3, Hans AR Bluyssen1, and Hein A. Koomans1

1 Department of Nephrology and Hypertension, Univiversity of Medical Center Utrecht, Utrecht, The Netherlands
2 Department of Molecular Cell Biology, University of Medical, Utrecht, The Netherlands
3 Genomic Laboratory, University of Medical Center Utrecht, Utrecht, The Netherlands

* To whom correspondence should be addressed. E-mail: g.b.braam{at}azu.nl.

The present study tested the hypothesis that acute increases in NO exert substantial influences on gene transcription in EC via guanylyl cyclase (GC). Human umbilical veins EC (HUVEC) were exposed to 0.1, 1 and 10 mM of sodium-nitroprusside (SNP) for 4 hours and to 1 mM SNP or 250 uM of DETA-NONOate for 2, 4, 8 and 24 hours. Also, cells were exposed to DETA-NONOate in the presence and absence of GC inhibitor 10 uM ODQ for 4 hours. RNA was isolated, reverse transcribed, Cy3- and Cy5-labeled and analyzed using cDNA microarrays. Increasing doses of SNP predominantly depressed gene expression in HUVEC. Genes function was related to growth, adhesion and cell structure. DETA-NONOate evoked a wave of expression changes (maximum at 4 hours), with a remarkable downregulation of the transcription factors MSX1, RELB and Egr-1. Both SNP- and DETA-NONOate-induced gene expression had faded after 24 hours, despite continued elevation of cGMP in the medium (of the SNP treated cells). Co-administration of ODQ decreased many, but not all of the transcriptional responses to DETA-NONOate. NO pronouncedly depressed EC gene expression, in particular of transcription factors. The observation that many, but not all, transcriptional changes induced by NO could be inhibited by inhibition of GC, indicates the presence of GC-independent NO actions on gene expression. Thus, EC gene expression responds to NO, however, the transcriptional response fades during prolonged exposure. This could allow the endothelial cell to respond to increased shear, without vigorous changes in gene expression.




This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
M. Y.K. Lee, H.-F. Tse, C.-W. Siu, S.-G. Zhu, R. Y.K. Man, and P. M. Vanhoutte
Genomic Changes in Regenerated Porcine Coronary Arterial Endothelial Cells
Arterioscler Thromb Vasc Biol, November 1, 2007; 27(11): 2443 - 2449.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
S. Wesseling, J. A. Joles, H. van Goor, H. A. Bluyssen, P. Kemmeren, F. C. Holstege, H. A. Koomans, and B. Braam
Transcriptome-based identification of pro- and antioxidative gene expression in kidney cortex of nitric oxide-depleted rats
Physiol Genomics, January 17, 2007; 28(2): 158 - 167.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
R. J. Dekker, R. A. Boon, M. G. Rondaij, A. Kragt, O. L. Volger, Y. W. Elderkamp, J. C. M. Meijers, J. Voorberg, H. Pannekoek, and A. J. G. Horrevoets
KLF2 provokes a gene expression pattern that establishes functional quiescent differentiation of the endothelium
Blood, June 1, 2006; 107(11): 4354 - 4363.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
H. Chon, M. C. Verhaar, H. A. Koomans, J. A. Joles, and B. Braam
Role of Circulating Karyocytes in the Initiation and Progression of Atherosclerosis
Hypertension, May 1, 2006; 47(5): 803 - 810.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
L. M. Bevers, B. Braam, J. A. Post, A. J. van Zonneveld, T. J. Rabelink, H. A. Koomans, M. C. Verhaar, and J. A. Joles
Tetrahydrobiopterin, but Not L-Arginine, Decreases NO Synthase Uncoupling in Cells Expressing High Levels of Endothelial NO Synthase
Hypertension, January 1, 2006; 47(1): 87 - 94.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
E. H. C. Tang, M. Feletou, Y. Huang, R. Y. K. Man, and P. M. Vanhoutte
Acetylcholine and sodium nitroprusside cause long-term inhibition of EDCF-mediated contractions
Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2434 - H2440.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
J. Hu, M. Kapoor, W. Zhang, S. R. Hamilton, and K. R. Coombes
Analysis of dose-response effects on gene expression data with comparison of two microarray platforms
Bioinformatics, September 1, 2005; 21(17): 3524 - 3529.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
B. Braam, R. de Roos, H. Bluyssen, P. Kemmeren, F. Holstege, J. A. Joles, and H. Koomans
Nitric Oxide-Dependent and Nitric Oxide-Independent Transcriptional Responses to High Shear Stress in Endothelial Cells
Hypertension, April 1, 2005; 45(4): 672 - 680.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.