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

Journal article
Authors C Rippe
S Albinsson
Gregor Guron
Holger Nilsson
K Swärd
Published in Acta physiologica (Oxford, England)
Volume 225
Issue 1
Pages e13094
ISSN 1748-1716
Publication year 2018
Published at Institute of Neuroscience and Physiology, Department of Physiology
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages e13094
Language en
Keywords GUCY1A1 GUCY1B1 hypertension remodelling smooth muscle stroke
Subject categories Physiology


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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