Elevated Adenosine Induces Placental DNA Hypomethylation Independent of A2B Receptor Signaling in Preeclampsia

Hypertension
Aji HuangYang Xia

Abstract

Preeclampsia is a prevalent pregnancy hypertensive disease with both maternal and fetal morbidity and mortality. Emerging evidence indicates that global placental DNA hypomethylation is observed in patients with preeclampsia and is linked to altered gene expression and disease development. However, the molecular basis underlying placental epigenetic changes in preeclampsia remains unclear. Using 2 independent experimental models of preeclampsia, adenosine deaminase-deficient mice and a pathogenic autoantibody-induced mouse model of preeclampsia, we demonstrate that elevated placental adenosine not only induces hallmark features of preeclampsia but also causes placental DNA hypomethylation. The use of genetic approaches to express an adenosine deaminase minigene specifically in placentas, or adenosine deaminase enzyme replacement therapy, restored placental adenosine to normal levels, attenuated preeclampsia features, and abolished placental DNA hypomethylation in adenosine deaminase-deficient mice. Genetic deletion of CD73 (an ectonucleotidase that converts AMP to adenosine) prevented the elevation of placental adenosine in the autoantibody-induced preeclampsia mouse model and ameliorated preeclampsia features and placental DNA...Continue Reading

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Citations

Jul 26, 2019·BioFactors·Amin KamraniMajid Ahmadi
Jan 14, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Takayuki IriyamaRodney E Kellems
Sep 29, 2019·Journal of Caffeine and Adenosine Research·Mariana Temido-FerreiraLuísa V Lopes
Sep 15, 2020·Policy Sciences·Kris Hartley, Minh Khuong Vu
Oct 2, 2021·Journal of Cellular Physiology·Lucas Sagrillo-FagundesMárcia R Wink
Oct 14, 2021·Clinical Science·Usman M AshrafBarbara T Alexander

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