Synthetic Receptors Induce Anti Angiogenic and Stress Signaling on Human First Trimester Cytotrophoblast Cells.

Ahmed Pantho,Mohammad Uddin,Mason Price,Thomas Kuehl,Umaima Wajid,Md Rhaman,Ahm Ashraf,Afsana Jahan,Syeda Afroze,Md Hossain,Maryam Khansari,Corey Johnson

doi:10.3390/ijerph14050517

Abstract

The cytotrophoblast (CTB) cells of the human placenta have membrane receptors that bind certain cardiotonic steroids (CTS) found in blood plasma. One of these, marinobufagenin, is a key factor in the etiology of preeclampsia. Herein, we used synthetic receptors (SR) to study their effectiveness on the angiogenic profile of human first trimester CTB cells. The humanextravillous CTB cells (Sw.71) used in this study were derived from first trimester chorionic villus tissue. Culture media of CTB cells treated with ≥1 nM SR level revealed sFlt-1 (Soluble fms-like tyrosine kinase-1) was significantly increased while VEGF (vascular endothelial growth factor) was significantly decreased in the culture media (* p < 0.05 for each) The AT2 receptor (Angiotensin II receptor type 2) expression was significantly upregulated in ≥1 nM SR-treated CTB cells as compared to basal; however, the AT1 (Angiotensin II receptor, type 1) and VEGFR-1 (vascular endothelial growth factor receptor 1) receptor expression was significantly downregulated (* p < 0.05 for each). Our results show that the anti-proliferative and anti-angiogenic effects of SR on CTB cells are similar to the effects of CTS. The observed anti angiogenic activity of SR on CTB cells demonstrates that the functionalized-urea/thiourea molecules may be useful as potent inhibitors to prevent CTS-induced impairment of CTB cells.

Highlights

IntroductionPreeclampsia (preE) [1] is a hypertensive disorder of pregnancy characterized by hypertension (diastolic ≥90 mmHg) and proteinuria (≥300 mg in 24 h) after 20 weeks of gestation
Preeclampsia [1] is a hypertensive disorder of pregnancy characterized by hypertension and proteinuria (≥300 mg in 24 h) after 20 weeks of gestation
The secretion of VEGF was inhibited in the culture media of CTB cells treated with ≥1 nM of VEGF was in thewhile culture of CTB factors cells treated

Summary

Introduction

Preeclampsia (preE) [1] is a hypertensive disorder of pregnancy characterized by hypertension (diastolic ≥90 mmHg) and proteinuria (≥300 mg in 24 h) after 20 weeks of gestation. 5–10% of pregnancies [2]. PreE is the second leading cause of maternal and fetal morbidity and mortality in the world [3,4,5,6]. The incidence of preE has risen in the U.S [7,8]. PreE is often accompanied by intrauterine growth restriction (IUGR) and is associated with preterm birth. Both of the latter conditions prejudice the survival and well being of the fetus [9].

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