Vogtmann, Rebekka and Heupel, Jacqueline and Herse, Florian and Matin, Mahsa and Hagmann, Henning and Bendix, Ivo and Kraeker, Kristin and Dechend, Ralf and Winterhager, Elke and Kimmig, Rainer and Koeninger, Angela and Gellhaus, Alexandra (2021) Circulating Maternal sFLT1 (Soluble fms-Like Tyrosine Kinase-1) Is Sufficient to Impair Spiral Arterial Remodeling in a Preeclampsia Mouse Model. HYPERTENSION, 78 (4). pp. 1067-1079. ISSN 0194-911X, 1524-4563
Full text not available from this repository. (Request a copy)Abstract
One driving factor for developing preeclampsia-a pregnancy disorder, often associated with poor spiral artery (SpA)-remodeling and fetal growth restriction-is the anti-angiogenic sFLT1 (soluble fms-like tyrosine kinase-1), which is found to be highly upregulated in preeclampsia patients. The sFLT1-mediated endothelial dysfunction is a common theory for the manifestation of maternal preeclampsia symptoms. However, the influence of sFLT1 on SpA-remodeling and the link between placental and maternal preeclampsia symptoms is less understood. To dissect the hsFLT1 (human sFLT1) effects on maternal and/or fetoplacental physiology in preeclampsia, sFLT1-transgenic mice with systemic hsFLT1 overexpression from midgestation onwards were used. SpA-remodeling was analyzed on histological and molecular level in placental/mesometrial triangle tissues. Maternal kidney and aorta morphology was investigated, combined with blood pressure measurements via telemetry. hsFLT1 overexpression resulted in maternal hypertension, aortic wall thickening, and elastin breakdown. Furthermore, maternal kidneys showed glomerular endotheliosis, podocyte damage, and proteinuria. preeclampsia symptoms were combined with fetal growth restriction already at the end of the second trimester and SpA-remodeling was strongly impaired as shown by persisted vascular smooth muscle cells. This phenotype was associated with shallow trophoblast invasion, delayed presence of uterine natural killer cells, and altered lymphatic angiogenesis. Overall, this study showed that circulating maternal hsFLT1 is sufficient to induce typical maternal preeclampsia-like symptoms in mice and impair the SpA-remodeling independent from the fetoplacental compartment, revealing new insights into the interaction between the placental and maternal contribution of preeclampsia.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANGIOGENIC FACTORS; EXPRESSION; PREGNANCY; INHIBITION; PREDICTION; PERFUSION; PRESSURE; PLACENTA; hypertension; mice; placenta; pregnancy; trophoblast |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Geburtshilfe) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Sep 2022 12:47 |
| Last Modified: | 30 Sep 2022 12:47 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48125 |
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