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

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 ex...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Catarina Rippe, Baoyi Zhu, Katarzyna K. Krawczyk, Ed. Van Bavel, Sebastian Albinsson, Jonas Sjölund, Erik N. T. P. Bakker, Karl Swärd
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d66f40af06af400e8dc806dbae39c231
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d66f40af06af400e8dc806dbae39c231
record_format	dspace
spelling	oai:doaj.org-article:d66f40af06af400e8dc806dbae39c2312021-12-02T11:52:26ZHypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway10.1038/s41598-017-01392-12045-2322https://doaj.org/article/d66f40af06af400e8dc806dbae39c2312017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01392-1https://doaj.org/toc/2045-2322Abstract 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.Catarina RippeBaoyi ZhuKatarzyna K. KrawczykEd. Van BavelSebastian AlbinssonJonas SjölundErik N. T. P. BakkerKarl SwärdNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Catarina Rippe Baoyi Zhu Katarzyna K. Krawczyk Ed. Van Bavel Sebastian Albinsson Jonas Sjölund Erik N. T. P. Bakker Karl Swärd Hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway
description	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 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.
format	article
author	Catarina Rippe Baoyi Zhu Katarzyna K. Krawczyk Ed. Van Bavel Sebastian Albinsson Jonas Sjölund Erik N. T. P. Bakker Karl Swärd
author_facet	Catarina Rippe Baoyi Zhu Katarzyna K. Krawczyk Ed. Van Bavel Sebastian Albinsson Jonas Sjölund Erik N. T. P. Bakker Karl Swärd
author_sort	Catarina Rippe
title	Hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway
title_short	Hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway
title_full	Hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway
title_fullStr	Hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway
title_full_unstemmed	Hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway
title_sort	hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the notch signaling pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d66f40af06af400e8dc806dbae39c231
work_keys_str_mv	AT catarinarippe hypertensionreducessolubleguanylylcyclaseexpressioninthemouseaortaviathenotchsignalingpathway AT baoyizhu hypertensionreducessolubleguanylylcyclaseexpressioninthemouseaortaviathenotchsignalingpathway AT katarzynakkrawczyk hypertensionreducessolubleguanylylcyclaseexpressioninthemouseaortaviathenotchsignalingpathway AT edvanbavel hypertensionreducessolubleguanylylcyclaseexpressioninthemouseaortaviathenotchsignalingpathway AT sebastianalbinsson hypertensionreducessolubleguanylylcyclaseexpressioninthemouseaortaviathenotchsignalingpathway AT jonassjolund hypertensionreducessolubleguanylylcyclaseexpressioninthemouseaortaviathenotchsignalingpathway AT erikntpbakker hypertensionreducessolubleguanylylcyclaseexpressioninthemouseaortaviathenotchsignalingpathway AT karlsward hypertensionreducessolubleguanylylcyclaseexpressioninthemouseaortaviathenotchsignalingpathway
_version_	1718395073253605376

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

Ejemplares similares