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Circulating Maternal sFLT1 (Soluble fms-Like Tyrosine Kinase-1) Is Sufficient to Impair Spiral Arterial Remodeling in a Preeclampsia Mouse Model
- Source :
- Hypertension (Dallas, Tex. : 1979)
- Publication Year :
- 2021
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2021.
-
Abstract
- Supplemental Digital Content is available in the text.<br />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.
- Subjects :
- medicine.medical_specialty
Spiral artery
hypertension
mice
placenta
Angiogenesis
Medizin
Neovascularization, Physiologic
Vascular Remodeling
Preeclampsia
Pre-Eclampsia
Pregnancy
Internal medicine
Placenta
Internal Medicine
medicine
Animals
Maternal hypertension
Endothelial dysfunction
reproductive and urinary physiology
Vascular Endothelial Growth Factor Receptor-1
business.industry
Original Articles
medicine.disease
trophoblast
female genital diseases and pregnancy complications
Disease Models, Animal
Endocrinology
medicine.anatomical_structure
Cardiovascular and Metabolic Diseases
embryonic structures
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING
Female
Hypoxia-Inducible Factor 1
business
Soluble fms-like tyrosine kinase-1
Pregnancy disorder
Subjects
Details
- ISSN :
- 15244563 and 0194911X
- Volume :
- 78
- Database :
- OpenAIRE
- Journal :
- Hypertension
- Accession number :
- edsair.doi.dedup.....944e571660e0c00b046f189a832f57bf