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Hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway

Rippe, Catarina LU ; Zhu, Baoyi LU ; Krawczyk, Katarzyna K. LU ; van Bavel, Ed; Albinsson, Sebastian LU ; Sjölund, Jonas LU ; Bakker, Erik N T P and Swärd, Karl LU (2017) In Scientific Reports 7(1).
Abstract

Hypertension is a dominating risk factor for cardiovascular disease. To characterize the genomic response to hypertension, we administered vehicle or angiotensin II to mice and performed gene expression analyses. AngII treatment resulted in a robust increase in blood pressure and altered expression of 235 genes in the aorta, including Gucy1a3 and Gucy1b3 which encode subunits of soluble guanylyl cyclase (sGC). Western blotting and immunohistochemistry confirmed repression of sGC associated with curtailed relaxation via sGC activation. Analysis of transcription factor binding motifs in promoters of differentially expressed genes identified enrichment of motifs for RBPJ, a component of the Notch signaling pathway, and the Notch... (More)

Hypertension is a dominating risk factor for cardiovascular disease. To characterize the genomic response to hypertension, we administered vehicle or angiotensin II to mice and performed gene expression analyses. AngII treatment resulted in a robust increase in blood pressure and altered expression of 235 genes in the aorta, including Gucy1a3 and Gucy1b3 which encode subunits of soluble guanylyl cyclase (sGC). Western blotting and immunohistochemistry confirmed repression of sGC associated with curtailed relaxation via sGC activation. Analysis of transcription factor binding motifs in promoters of differentially expressed genes identified enrichment of motifs for RBPJ, a component of the Notch signaling pathway, and the Notch coactivators FRYL and MAML2 were reduced. Gain and loss of function experiments demonstrated that JAG/NOTCH signaling controls sGC expression together with MAML2 and FRYL. Reduced expression of sGC, correlating with differential expression of MAML2, in stroke prone and spontaneously hypertensive rats was also seen, and RNA-Seq data demonstrated correlations between JAG1, NOTCH3, MAML2 and FRYL and the sGC subunits GUCY1A3 and GUCY1B3 in human coronary artery. Notch signaling thus provides a constitutive drive on expression of the major nitric oxide receptor (GUCY1A3/GUCY1B3) in arteries from mice, rats, and humans, and this control mechanism is disturbed in hypertension.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
7
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85018280054
  • wos:000400449700009
ISSN
2045-2322
DOI
10.1038/s41598-017-01392-1
language
English
LU publication?
yes
id
44d8a8ed-a8a4-499c-99db-bb2c61ea21d4
date added to LUP
2017-05-17 08:16:31
date last changed
2017-09-18 11:35:55
@article{44d8a8ed-a8a4-499c-99db-bb2c61ea21d4,
  abstract     = {<p>Hypertension is a dominating risk factor for cardiovascular disease. To characterize the genomic response to hypertension, we administered vehicle or angiotensin II to mice and performed gene expression analyses. AngII treatment resulted in a robust increase in blood pressure and altered expression of 235 genes in the aorta, including Gucy1a3 and Gucy1b3 which encode subunits of soluble guanylyl cyclase (sGC). Western blotting and immunohistochemistry confirmed repression of sGC associated with curtailed relaxation via sGC activation. Analysis of transcription factor binding motifs in promoters of differentially expressed genes identified enrichment of motifs for RBPJ, a component of the Notch signaling pathway, and the Notch coactivators FRYL and MAML2 were reduced. Gain and loss of function experiments demonstrated that JAG/NOTCH signaling controls sGC expression together with MAML2 and FRYL. Reduced expression of sGC, correlating with differential expression of MAML2, in stroke prone and spontaneously hypertensive rats was also seen, and RNA-Seq data demonstrated correlations between JAG1, NOTCH3, MAML2 and FRYL and the sGC subunits GUCY1A3 and GUCY1B3 in human coronary artery. Notch signaling thus provides a constitutive drive on expression of the major nitric oxide receptor (GUCY1A3/GUCY1B3) in arteries from mice, rats, and humans, and this control mechanism is disturbed in hypertension.</p>},
  articleno    = {1334},
  author       = {Rippe, Catarina and Zhu, Baoyi and Krawczyk, Katarzyna K. and van Bavel, Ed and Albinsson, Sebastian and Sjölund, Jonas and Bakker, Erik N T P and Swärd, Karl},
  issn         = {2045-2322},
  language     = {eng},
  month        = {05},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway},
  url          = {http://dx.doi.org/10.1038/s41598-017-01392-1},
  volume       = {7},
  year         = {2017},
}