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RNA interference therapeutics targeting angiotensinogen ameliorate preeclamptic phenotype in rodent models
Nadine Haase, … , Babbette LaMarca, Ralf Dechend
Nadine Haase, … , Babbette LaMarca, Ralf Dechend
Published April 27, 2020
Citation Information: J Clin Invest. 2020;130(6):2928-2942. https://doi.org/10.1172/JCI99417.
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Research Article Reproductive biology

RNA interference therapeutics targeting angiotensinogen ameliorate preeclamptic phenotype in rodent models

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Abstract

Authors

Nadine Haase, Donald J. Foster, Mark W. Cunningham, Julia Bercher, Tuyen Nguyen, Svetlana Shulga-Morskaya, Stuart Milstein, Sarfraz Shaikh, Jeff Rollins, Michaela Golic, Florian Herse, Kristin Kräker, Ivo Bendix, Meray Serdar, Hanna Napieczynska, Arnd Heuser, Alexandra Gellhaus, Kristin Thiele, Gerd Wallukat, Dominik N. Müller, Babbette LaMarca, Ralf Dechend

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Figure 1

siRNA does not cross the placental barrier.

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siRNA does not cross the placental barrier.
(A) Effect of luciferase-tar...
(A) Effect of luciferase-targeting siRNA or hAgt-targeting siRNA on hAgt mRNA expression levels in maternal liver and kidney tissue of preeclamptic (PE) rats. hAgt expression was significantly reduced in maternal liver but not in maternal kidney (n = 5 each; *P < 0.05; Mann-Whitney test; mean ± SEM). (B) Effect of luciferase-targeting siRNA or hAgt-targeting siRNA on rAgt mRNA expression levels in maternal liver and kidney tissue of PE rats. rAgt expression was unaffected in maternal liver and kidney by siRNA (n = 5 each; mean ± SEM). (C) Effect of luciferase-targeting siRNA or hAgt-targeting siRNA on hAgt mRNA expression levels in mesometrial triangle, placenta, and fetal tissue in PE rats. hAgt expression was not suppressed by hAgt-targeting siRNA in mesometrial triangle, placenta, fetal liver, fetal kidney, or fetal brain. Expression level of hAgt was higher in fetal liver of hAgt-targeting versus luciferase-targeting siRNA–treated rats (n = 5 each; *P < 0.05, **P < 0.01; unpaired t test; mean ± SEM). (D) Effect of luciferase-targeting siRNA or hAgt-targeting siRNA on rAgt mRNA expression levels in mesometrial triangle, placenta, and fetal tissue of PE rats. rAgt expression was unaffected in mesometrial triangle, placenta, fetal kidney, and fetal brain by siRNA. Expression level of rAgt was higher in fetal liver of hAgt-targeting versus luciferase-targeting siRNA–treated rats (n = 5 each; **P < 0.01; Mann-Whitney test; mean ± SEM). (E) Distribution of hAgt-targeting siRNA in PE rats after treatment. The highest amount of siRNA could be detected in the maternal liver (n = 4), whereas the amount of siRNA was lower in placental compared with maternal liver (n = 4; **P < 0.01; 1-way ANOVA with Tukey’s post hoc test; mean ± SEM) and none was detectable in fetal liver (n = 8). LOD, limit of detection.

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