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Targeting transcriptional control of soluble guanylyl cyclase via NOTCH for prevention of cardiovascular disease

Rippe, C. LU ; Albinsson, S. LU ; Guron, G.; Nilsson, H. and Swärd, K. LU (2018) In Acta Physiologica
Abstract

Soluble guanylyl cyclase (sGC) is an effector enzyme of nitric oxide (NO). Recent work has unravelled how levels of this enzyme are controlled, and highlighted a role in vascular disease. We provide a timely summary of available knowledge on transcriptional regulation of sGC, including influences from the NOTCH signalling pathway and genetic variants. It is speculated that hypertension-induced repression of sGC starts a vicious circle that can be initiated by periods of stress, diet or genetic factors, and a key tenet is that reduction in sGC further raises blood pressure. The idea that dysregulation of sGC contributes to syndromes caused by defective NOTCH signalling is advanced, and we discuss drug repositioning for vascular disease... (More)

Soluble guanylyl cyclase (sGC) is an effector enzyme of nitric oxide (NO). Recent work has unravelled how levels of this enzyme are controlled, and highlighted a role in vascular disease. We provide a timely summary of available knowledge on transcriptional regulation of sGC, including influences from the NOTCH signalling pathway and genetic variants. It is speculated that hypertension-induced repression of sGC starts a vicious circle that can be initiated by periods of stress, diet or genetic factors, and a key tenet is that reduction in sGC further raises blood pressure. The idea that dysregulation of sGC contributes to syndromes caused by defective NOTCH signalling is advanced, and we discuss drug repositioning for vascular disease prevention. The advantage of targeting sGC expression rather than activity is also considered. It is argued that transcriptional inputs on sGC arise from interactions with other cells, the extracellular matrix and microRNAs (miRNAs), and concluded that the promise of sGC as a target for prevention of cardiovascular disease has increased in recent time.

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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
GUCY1A1, GUCY1B1, Hypertension, Remodelling, Smooth muscle, Stroke
in
Acta Physiologica
publisher
Wiley-Blackwell
external identifiers
  • scopus:85047728931
ISSN
1748-1708
DOI
10.1111/apha.13094
language
English
LU publication?
yes
id
be399991-c787-4ef2-b10e-c954205ce712
date added to LUP
2018-06-15 14:29:14
date last changed
2018-06-16 03:00:04
@article{be399991-c787-4ef2-b10e-c954205ce712,
  abstract     = {<p>Soluble guanylyl cyclase (sGC) is an effector enzyme of nitric oxide (NO). Recent work has unravelled how levels of this enzyme are controlled, and highlighted a role in vascular disease. We provide a timely summary of available knowledge on transcriptional regulation of sGC, including influences from the NOTCH signalling pathway and genetic variants. It is speculated that hypertension-induced repression of sGC starts a vicious circle that can be initiated by periods of stress, diet or genetic factors, and a key tenet is that reduction in sGC further raises blood pressure. The idea that dysregulation of sGC contributes to syndromes caused by defective NOTCH signalling is advanced, and we discuss drug repositioning for vascular disease prevention. The advantage of targeting sGC expression rather than activity is also considered. It is argued that transcriptional inputs on sGC arise from interactions with other cells, the extracellular matrix and microRNAs (miRNAs), and concluded that the promise of sGC as a target for prevention of cardiovascular disease has increased in recent time.</p>},
  author       = {Rippe, C. and Albinsson, S. and Guron, G. and Nilsson, H. and Swärd, K.},
  issn         = {1748-1708},
  keyword      = {GUCY1A1,GUCY1B1,Hypertension,Remodelling,Smooth muscle,Stroke},
  language     = {eng},
  month        = {05},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Physiologica},
  title        = {Targeting transcriptional control of soluble guanylyl cyclase via NOTCH for prevention of cardiovascular disease},
  url          = {http://dx.doi.org/10.1111/apha.13094},
  year         = {2018},
}