4.8 Article Publication with Expression of Concern

Regulator of G protein signaling 5 is a determinant of gestational hypertension and preeclampsia (Publication with Expression of Concern. See vol. 12, 2020)

Journal

SCIENCE TRANSLATIONAL MEDICINE
Volume 7, Issue 290, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aaa5038

Keywords

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Funding

  1. Royal Perth Hospital Medical Research Foundation
  2. Harry Perkins Institute of Medical Research
  3. National Health and Medical Research Council of Australia [APP1042446, 0546087, 634304]
  4. Australian government
  5. University of Western Australia
  6. National Health and Medical Research Council of Australia [634304] Funding Source: NHMRC

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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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