Universität zu Köln

Vogtmann, Rebekka ORCID: 0000-0002-8491-500X, Heupel, Jacqueline, Herse, Florian, Matin, Mahsa, Hagmann, Henning, Bendix, Ivo ORCID: 0000-0002-9751-3640, Kraeker, Kristin, Dechend, Ralf, Winterhager, Elke, Kimmig, Rainer, 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). S. 1067 - 1080. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1524-4563

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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:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vogtmann, Rebekka UNSPECIFIED orcid.org/0000-0002-8491-500X UNSPECIFIED Heupel, Jacqueline UNSPECIFIED UNSPECIFIED UNSPECIFIED Herse, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Matin, Mahsa UNSPECIFIED UNSPECIFIED UNSPECIFIED Hagmann, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Bendix, Ivo UNSPECIFIED orcid.org/0000-0002-9751-3640 UNSPECIFIED Kraeker, Kristin UNSPECIFIED UNSPECIFIED UNSPECIFIED Dechend, Ralf UNSPECIFIED UNSPECIFIED UNSPECIFIED Winterhager, Elke UNSPECIFIED UNSPECIFIED UNSPECIFIED Kimmig, Rainer UNSPECIFIED UNSPECIFIED UNSPECIFIED Koeninger, Angela UNSPECIFIED UNSPECIFIED UNSPECIFIED Gellhaus, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-599228
DOI:	10.1161/HYPERTENSIONAHA.121.17567
Journal or Publication Title:	Hypertension
Volume:	78
Number:	4
Page Range:	S. 1067 - 1080
Date:	2021
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	1524-4563
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANGIOGENIC FACTORS; EXPRESSION; PREGNANCY; INHIBITION; PREDICTION; PERFUSION; PRESSURE; PLACENTA Multiple languages Peripheral Vascular Disease Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59922