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Genetic modifiers of hypertension in soluble guanylate cyclase α1-deficient mice

Emmanuel S Buys, Michael J Raher, Andrew Kirby, Mohd Shahid, David M Baron, Sarah R Hayton, Laurel T Tainsh, Patrick Y Sips, Kristen M Rauwerdink and Qingshang Yan, et al. (2012) JOURNAL OF CLINICAL INVESTIGATION. 122(6). p.2316-2325
abstract
Nitric oxide (NO) plays an essential role in regulating hypertension and blood flow by inducing relaxation of vascular smooth muscle. Male mice deficient in a NO receptor component, the α1 subunit of soluble guanylate cyclase (sGCα1), are prone to hypertension in some, but not all, mouse strains, suggesting that additional genetic factors contribute to the onset of hypertension. Using linkage analyses, we discovered a quantitative trait locus (QTL) on chromosome 1 that was linked to mean arterial pressure (MAP) in the context of sGCα1 deficiency. This region is syntenic with previously identified blood pressure-related QTLs in the human and rat genome and contains the genes coding for renin. Hypertension was associated with increased activity of the renin-angiotensin-aldosterone system (RAAS). Further, we found that RAAS inhibition normalized MAP and improved endothelium-dependent vasorelaxation in sGCα1-deficient mice. These data identify the RAAS as a blood pressure-modifying mechanism in a setting of impaired NO/cGMP signaling.
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author
organization
alternative title
Genetic modifiers of hypertension in soluble guanylate cyclase alpha 1-deficient mice
year
type
journalArticle (original)
publication status
published
subject
keyword
BLOOD-PRESSURE REGULATION, QUANTITATIVE TRAIT LOCI, GENOME-WIDE ASSOCIATION, TGR(MREN2) 27 RATS, KNOCKOUT MICE, SMOOTH-MUSCLE-CELLS, KIDNEY-DISEASE, CONVERTING ENZYME, NITRIC-OXIDE SYNTHASE, RENIN-ANGIOTENSIN SYSTEM
journal title
JOURNAL OF CLINICAL INVESTIGATION
J. Clin. Invest.
volume
122
issue
6
pages
2316 - 2325
Web of Science type
Article
Web of Science id
000304736300038
JCR category
MEDICINE, RESEARCH & EXPERIMENTAL
JCR impact factor
12.812 (2012)
JCR rank
4/119 (2012)
JCR quartile
1 (2012)
ISSN
0021-9738
DOI
10.1172/JCI60119
language
English
UGent publication?
yes
classification
A1
additional info
correction published in J. Clin. Invest. (2012) 122(8), 3024 ; DOI 10.1172/JCI65763 [author name]
copyright statement
I have transferred the copyright for this publication to the publisher
id
2138459
handle
http://hdl.handle.net/1854/LU-2138459
date created
2012-06-11 12:07:10
date last changed
2013-01-11 14:28:03
@article{2138459,
  abstract     = {Nitric oxide (NO) plays an essential role in regulating hypertension and blood flow by inducing relaxation of vascular smooth muscle. Male mice deficient in a NO receptor component, the \ensuremath{\alpha}1 subunit of soluble guanylate cyclase (sGC\ensuremath{\alpha}1), are prone to hypertension in some, but not all, mouse strains, suggesting that additional genetic factors contribute to the onset of hypertension. Using linkage analyses, we discovered a quantitative trait locus (QTL) on chromosome 1 that was linked to mean arterial pressure (MAP) in the context of sGC\ensuremath{\alpha}1 deficiency. This region is syntenic with previously identified blood pressure-related QTLs in the human and rat genome and contains the genes coding for renin. Hypertension was associated with increased activity of the renin-angiotensin-aldosterone system (RAAS). Further, we found that RAAS inhibition normalized MAP and improved endothelium-dependent vasorelaxation in sGC\ensuremath{\alpha}1-deficient mice. These data identify the RAAS as a blood pressure-modifying mechanism in a setting of impaired NO/cGMP signaling.},
  author       = {Buys, Emmanuel S and Raher, Michael J and Kirby, Andrew and Shahid, Mohd and Baron, David M and Hayton, Sarah R and Tainsh, Laurel T and Sips, Patrick Y and Rauwerdink, Kristen M and Yan, Qingshang and Tainsh, Robert ET and Shakartzi, Hannah R and Stevens, Christine and Decaluw{\'e}, Kelly and Rodrigues-Machado, Maria da Gloria and Malhotra, Rajeev and Van de Voorde, Johan and Wang, Tong and Brouckaert, Peter and Daly, Mark J and Bloch, Kenneth D},
  issn         = {0021-9738},
  journal      = {JOURNAL OF CLINICAL INVESTIGATION},
  keyword      = {BLOOD-PRESSURE REGULATION,QUANTITATIVE TRAIT LOCI,GENOME-WIDE ASSOCIATION,TGR(MREN2) 27 RATS,KNOCKOUT MICE,SMOOTH-MUSCLE-CELLS,KIDNEY-DISEASE,CONVERTING ENZYME,NITRIC-OXIDE SYNTHASE,RENIN-ANGIOTENSIN SYSTEM},
  language     = {eng},
  number       = {6},
  pages        = {2316--2325},
  title        = {Genetic modifiers of hypertension in soluble guanylate cyclase \ensuremath{\alpha}1-deficient mice},
  url          = {http://dx.doi.org/10.1172/JCI60119},
  volume       = {122},
  year         = {2012},
}

Chicago
Buys, Emmanuel S, Michael J Raher, Andrew Kirby, Mohd Shahid, David M Baron, Sarah R Hayton, Laurel T Tainsh, et al. 2012. “Genetic Modifiers of Hypertension in Soluble Guanylate Cyclase Α1-deficient Mice.” Journal of Clinical Investigation 122 (6): 2316–2325.
APA
Buys, E. S., Raher, M. J., Kirby, A., Shahid, M., Baron, D. M., Hayton, S. R., Tainsh, L. T., et al. (2012). Genetic modifiers of hypertension in soluble guanylate cyclase α1-deficient mice. JOURNAL OF CLINICAL INVESTIGATION, 122(6), 2316–2325.
Vancouver
1.
Buys ES, Raher MJ, Kirby A, Shahid M, Baron DM, Hayton SR, et al. Genetic modifiers of hypertension in soluble guanylate cyclase α1-deficient mice. JOURNAL OF CLINICAL INVESTIGATION. 2012;122(6):2316–25.
MLA
Buys, Emmanuel S, Michael J Raher, Andrew Kirby, et al. “Genetic Modifiers of Hypertension in Soluble Guanylate Cyclase Α1-deficient Mice.” JOURNAL OF CLINICAL INVESTIGATION 122.6 (2012): 2316–2325. Print.