1. Placental hypoxia-induced alterations in vascular function, morphology, and endothelial barrier integrity
- Author
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Aalt Bast, Ger M.J. Janssen, Philippe Vangrieken, Ulrike von Rango, Salwan Al-Nasiry, Daan Vroomans, Frederik J. van Schooten, Alexander Remels, Yannick C W Pinckers, Paul M. H. Schiffers, RS: NUTRIM - R3 - Respiratory & Age-related Health, Farmacologie en Toxicologie, Obstetrie & Gynaecologie, MUMC+: MA Medische Staf Obstetrie Gynaecologie (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, FSE Campus Venlo, RS: FSE UCV Adaptive responses in relation to health effect and safety of nutrition, Anatomie & Embryologie, and RS: Carim - V02 Hypertension and target organ damage
- Subjects
Vascular smooth muscle ,Physiology ,Placenta ,030204 cardiovascular system & hematology ,medicine.disease_cause ,0302 clinical medicine ,Pre-Eclampsia ,Pregnancy ,030212 general & internal medicine ,OXIDATIVE STRESS ,Hypoxia ,VITAMIN-E ,Electrical impedance myography ,Chemistry ,WOMEN ,Endothelial stem cell ,medicine.anatomical_structure ,Hypertension ,embryonic structures ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,Endothelium ,HYPERTENSIVE PREGNANCY ,PATHOPHYSIOLOGY ,In Vitro Techniques ,Permeability ,Cell Line ,Preeclampsia ,03 medical and health sciences ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Placental hypoxia ,UTERINE PERFUSION ,Endothelial Cells ,Hypoxia (medical) ,ANTIANGIOGENIC FACTORS ,medicine.disease ,DYSFUNCTION ,Endocrinology ,Vasoconstriction ,15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid ,Culture Media, Conditioned ,CELLS ,Endothelium, Vascular ,Reactive Oxygen Species ,Oxidative stress - Abstract
Preeclampsia (PE) is a pregnancy-related disorder characterized by hypertension and proteinuria that affects 3-10% of all pregnancies. Although its pathophysiology remains obscure, placental hypoxia-induced oxidative stress and alterations in vascular function, morphology, and endothelial barrier integrity are considered to play a key role in the development of preeclampsia. In this study, placental villous explants of noncomplicated placentae and BeWo cells were subjected to hypoxia. The effect of placental hypoxic-conditioned medium (HCM) on intraluminal-induced contraction and endothelial barrier integrity in chorionic arteries was investigated using pressure myography. The impact of BeWo cell HCM on endothelial cell viability, reactive oxygen species formation and inflammation was also determined. Alterations in arterial morphology and contractile responsiveness to the thromboxane A2 analog (U46619) after exposure to placental HCM were examined immunohistochemically and by wire myography, respectively. Intraluminal administration of placental HCM induced vasoconstriction and increased the endothelial permeability for KCl, which was concentration-dependently prevented by quercetin. Placental and BeWo cell HCMs decreased endothelial cell viability, increased the production of reactive oxygen species and enhanced the secretion of IL-6 and IL-8. The cross-sectional area of the arterial media was increased upon exposure to placental HCM, which was associated with increased vascular proliferation and contractile responsiveness to U46619, and all of these effects were prevented by the antioxidants quercetin and RRR-alpha-tocopherol. This study is the first to comprehensively demonstrate the link between factors secreted by placental cells in response to hypoxia and vascular abnormalities and paves the way for new diagnostic approaches and therapies to better protect the maternal vasculature during and after a preeclampsia-complicated pregnancy.
- Published
- 2020