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

Authors

Vasyl Holobotovskyy, University of Western Australia
Yee Seng Chong, University of Western Australia
Jennifer Burchell, University of Western Australia
Bo He, University of Western Australia
Michael Phillips, University of Western Australia
Leo Leader, University of Western Australia
Timothy Murphy, University of New South Wales
Shaun L. Sandow, University of New South WalesFollow
Douglas J. McKitrick, University of Western Australia
Adrian K. Charles, University of Western Australia
Marianne Tare, Monash University
Leonard F. Arnolda, Canberra HospitalFollow
Ruth Ganss, University of Western Australia

RIS ID

106970

Publication Details

Holobotovskyy, V., Chong, Y., Burchell, J., He, B., Phillips, M., Leader, L., Murphy, T., Sandow, S. L., McKitrick, D. J., Charles, A. K., Tare, M., Arnolda, L. F. & Ganss, R. (2015). Regulator of G protein signaling 5 is a determinant of gestational hypertension and preeclampsia. Science Translational Medicine, 7 (290), 290ra88-1-290ra88-11.

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.