Research ArticlePreeclampsia

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

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Science Translational Medicine  03 Jun 2015:
Vol. 7, Issue 290, pp. 290ra88
DOI: 10.1126/scitranslmed.aaa5038

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Drugs may play a PPARt against preeclampsia

Preeclampsia is a vascular disorder of pregnancy, with symptoms including hypertension and loss of protein in the urine. The underlying causes of preeclampsia are not yet understood, and the only effective treatment is preterm delivery of the infant, which poses many risks for the child. Holobotovskyy et al. determined that a vascular protein called RGS5 plays an important role in the regulation of blood pressure during pregnancy and that a lack of this protein causes a preeclampsia-like syndrome in mouse models. These mice could be effectively treated with drugs called PPAR agonists, some of which are already approved for diabetes in humans, suggesting a potential therapeutic approach for 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.

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