title: Regulator of G protein signaling 5 is a determinant of gestational hypertension and preeclampsia.
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.
authors.affiliation: Harry Perkins Institute of Medical Research, Centre for Medical Research, The University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors.forename: Vasyl
authors.initials: V
authors.lastname: Holobotovskyy
authors.affiliation: Harry Perkins Institute of Medical Research, Centre for Medical Research, The University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors.forename: Yee Seng
authors.initials: YS
authors.lastname: Chong
authors.affiliation: Harry Perkins Institute of Medical Research, Centre for Medical Research, The University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Burchell
authors.affiliation: Harry Perkins Institute of Medical Research, Centre for Medical Research, The University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors.forename: Bo
authors.initials: B
authors.lastname: He
authors.affiliation: Harry Perkins Institute of Medical Research, Centre for Medical Research, The University of Western Australia, Nedlands, Western Australia 6009, Australia. Royal Perth Hospital, Perth, Western Australia 6009, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Phillips
authors.affiliation: School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2031, Australia.
authors.forename: Leo
authors.initials: L
authors.lastname: Leader
authors.affiliation: Physiology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia.
authors.forename: Timothy V
authors.initials: TV
authors.lastname: Murphy
authors.affiliation: Physiology, School of Medical Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia. Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Maroochydore, Queensland 4558, Australia.
authors.forename: Shaun L
authors.initials: SL
authors.lastname: Sandow
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia & Cardiology Department, Royal Perth Hospital, Perth, Western Australia 6000, Australia.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: McKitrick
authors.affiliation: Princess Margaret Hospital and School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia 6008, Australia.
authors.forename: Adrian K
authors.initials: AK
authors.lastname: Charles
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria 3800, Australia. School of Rural Health, Monash University, Churchill, Victoria 3842, Australia.
authors.forename: Marianne
authors.initials: M
authors.lastname: Tare
authors.affiliation: Medical School, Australian National University, and Cardiology Department, Canberra Hospital, Canberra, Australian Capital Territory 2606, Australia.
authors.forename: Leonard F
authors.initials: LF
authors.lastname: Arnolda
authors.affiliation: Harry Perkins Institute of Medical Research, Centre for Medical Research, The University of Western Australia, Nedlands, Western Australia 6009, Australia. ganss@perkins.uwa.edu.au.
authors.forename: Ruth
authors.initials: R
authors.lastname: Ganss
mesh_terms: D000222:Adaptation, Physiological; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D005260:Female; D051379:Mice; D018384:Oxidative Stress; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D020710:RGS Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D020710:RGS Proteins; C105346:Rgs5 protein, mouse; D000804:Angiotensin II