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| Status |
Public on May 01, 2017 |
| Title |
Hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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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| Overall design |
2 months old mice were implanted with miniosmotic pumps containing either angiotensin (1µg/kg/min) (n=8) or saline (n=7). After three weeks aorta was dissected and mRNA was extracted and samples were used for gene expression array.
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| Contributor(s) |
Swärd K, Rippe C |
| Citation(s) |
28465505 |
| Submission date |
Jan 13, 2017 |
| Last update date |
Feb 21, 2018 |
| Contact name |
Catarina Rippe |
| E-mail(s) |
catarina.rippe@med.lu.se
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| Organization name |
Lund University
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| Department |
Experimental Sciences
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| Street address |
BMC, D12
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| City |
Lund |
| ZIP/Postal code |
22184 |
| Country |
Sweden |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA361259 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE93597_RAW.tar |
133.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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