Regulator of G protein signaling 5 is a pivotal determinant of gestational hypertension and preeclampsia

V Holobotovskyy; Y S Chong; J Burchell; B He; Michael Phillips; L Leader; T V Murphy; Shaun L Sandow; D J McKitrick; A K Charles; M Tare; L F Arnolda; R Ganss

doi:10.1126/scitranslmed.aaa5038

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Regulator of G protein signaling 5 is a pivotal determinant of gestational hypertension and preeclampsia

Journal article

Peer reviewed

Regulator of G protein signaling 5 is a pivotal determinant of gestational hypertension and preeclampsia

V Holobotovskyy, Y S Chong, J Burchell, B He, Michael Phillips, L Leader, T V Murphy, Shaun L Sandow, D J McKitrick, A K Charles, …

Science Translational Medicine, Vol.7(290), p.290ra88

2015

DOI: https://doi.org/10.1126/scitranslmed.aaa5038

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Abstract

Preeclampsia is a systemic vascular disorder of pregnancy and is associated with increased sensitivity to angiotensin II (AngII) and hypertension. The cause of preeclampsia remains unknown. We identified the role of regulator of G protein (heterotrimeric guanine nucleotide-binding protein) signaling 5 (RGS5) in blood pressure regulation during pregnancy and preeclampsia. RGS5 expression in human myometrial vessels is markedly suppressed in gestational hypertension and/or preeclampsia. In pregnant RGS5-deficient mice, reduced vascular RGS5 expression causes gestational hypertension by enhancing vascular sensitivity to AngII. Further challenge by increasing AngII results in preeclampsia-like symptoms, namely, more severe hypertension, proteinuria, placental pathology, and reduced birth weight. In pregnant heterozygote null mice, treatment with peroxisome proliferator-activated receptor (PPAR) agonists normalizes vascular function and blood pressure through effects on RGS5. These findings highlight a key role of RGS5 at the interface between AngII and PPAR signaling. Because preeclampsia is refractory to current standard therapies, our study opens an unrecognized and urgently needed opportunity for treatment of gestational hypertension and preeclampsia.

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Title: Regulator of G protein signaling 5 is a pivotal determinant of gestational hypertension and preeclampsia
Authors: V Holobotovskyy (Author) - University of Western Australia
Y S Chong (Author) - University of Western Australia
J Burchell (Author) - University of Western Australia
B He (Author) - University of Western Australia
Michael Phillips (Author) - University of Western Australia
L Leader (Author) - University of New South Wales
T V Murphy (Author) - University of New South Wales
Shaun L Sandow (Author) - University of the Sunshine Coast - Faculty of Science, Health, Education and Engineering
D J McKitrick (Author) - University of Western Australia
A K Charles (Author) - University of Western Australia
M Tare (Author) - Monash University
L F Arnolda (Author) - Australian National University
R Ganss (Author) - University of Western Australia
Publication details: Science Translational Medicine, Vol.7(290), p.290ra88
Publisher: American Association for the Advancement of Science
Date published: 2015
DOI: 10.1126/scitranslmed.aaa5038
ISSN: 1946-6234
Organisation Unit: School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99449932202621
Output Type: Journal article

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Collaboration types: Domestic collaboration
Web Of Science research areas: Cell Biology; Medicine, Research & Experimental

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