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Inhibition of Trophoblast-Induced Spiral Artery Remodeling Reduces Placental Perfusion in Rat Pregnancy.

Verlohren, S; Geusens, N; Morton, J; Verhaegen, I; Hering, L; Herse, F; Dudenhausen, JW; Muller, DN; Luft, FC; Cartwright, JE; et al. Verlohren, S; Geusens, N; Morton, J; Verhaegen, I; Hering, L; Herse, F; Dudenhausen, JW; Muller, DN; Luft, FC; Cartwright, JE; Davidge, ST; Pijnenborg, R; Dechend, R (2010) Inhibition of Trophoblast-Induced Spiral Artery Remodeling Reduces Placental Perfusion in Rat Pregnancy. HYPERTENSION, 56 (2). 304 -310 (7). ISSN 0194-911X https://doi.org/10.1161/HYPERTENSIONAHA.110.153163
SGUL Authors: Cartwright, Judith Eleanor

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Abstract

Rats harboring the human angiotensinogen and human renin genes develop preeclamptic features in pregnancy. The preeclamptic rats exhibit a deeper trophoblast invasion associated with a reduced resistance index by uterine Doppler. Doxycycline inhibits matrix metalloproteinase activity. We tested the hypothesis that matrix metalloproteinase inhibition reduces trophoblast invasion with subsequent changes in placental perfusion. Preeclamptic and pregnant control Sprague-Dawley rats were treated with doxycycline (30 mg/kg of body weight orally) from gestational day 12 until day 18. Placental perfusion was assessed using a micromarker contrast agent. The animals were euthanized on day 18 of pregnancy; biometric data were acquired, and trophoblast invasion was analyzed. Doxycycline resulted in intrauterine growth retardation and lighter placentas in both groups. Maternal body weight was not affected. As shown earlier, preeclamptic rats exhibited a deeper endovascular trophoblast invasion. However, doxycycline treatment reduced trophoblast invasion in the preeclamptic rats. The physiological spiral artery remodeling, as assessed by the deposition of fibrinoid and α-actin in the spiral artery contour, was significantly reduced by doxycycline. The vascularity index, as assessed by perfusion measurement of the placenta, was reduced after doxycycline treatment in preeclamptic rats. Thus, matrix metalloproteinase inhibition with doxycycline leads to reduced trophoblast invasion and associated reduced placental perfusion. These studies are the first to show that reducing trophoblast-induced vascular remodeling decreases subsequent placental perfusion. Our model allows the study of dysregulated trophoblast invasion and vascular remodeling in vivo to gain important insights into preeclampsia-related mechanisms.

Item Type: Article
Additional Information: PubMed ID: 20606107
Keywords: Angiotensinogen, Animals, Apoptosis, Arteries, Blood Pressure, Female, Humans, Organ Size, Placenta, Pre-Eclampsia, Pregnancy, Rats, Rats, Sprague-Dawley, Reference Values, Renin, Systole, Trophoblasts, Science & Technology, Life Sciences & Biomedicine, Peripheral Vascular Disease, Cardiovascular System & Cardiology, pregnancy, trophoblast, rats, animal models, doxycycline, matrix metalloproteinases, preeclampsia, NATURAL-KILLER-CELLS, RENIN-ANGIOTENSIN SYSTEM, MATRIX METALLOPROTEINASES, BLOOD-FLOW, PREECLAMPSIA, INVASION, MODEL, DOXYCYCLINE, HYPERTENSION, LOCALIZATION, pregnancy, trophoblast, rats, animal models, doxycycline, matrix metalloproteinases, preeclampsia
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Vascular (INCCVA)
Journal or Publication Title: HYPERTENSION
ISSN: 0194-911X
Related URLs:
Dates:
DateEvent
1 August 2010Published
Web of Science ID: WOS:000279880200023
URI: https://openaccess.sgul.ac.uk/id/eprint/100953
Publisher's version: https://doi.org/10.1161/HYPERTENSIONAHA.110.153163

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