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Int. J. Environ. Res. Public Health 2017, 14(5), 517; doi:10.3390/ijerph14050517

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

1
Department of Biochemistry, University of Texas at Austin, Austin, TX 78712, USA
2
Department of Biology, Angelo State University, San Angelo, TX 76904, USA
3
Department of Obstetrics & Gynecology, Baylor Scott & White Health, Temple/Texas A&M Health Science Center College of Medicine, Temple, TX 76508, USA
4
Department of Chemistry & Biochemistry, Jackson State University, Jackson, MS 39217, USA
5
Medical Physiology, Texas A&M Health Science Center College of Medicine, Temple, TX 76504, USA
6
Department of Pediatrics, Baylor Scott & White Health, Temple/Texas A&M Health Science Center College of Medicine, Temple, TX 76508, USA
7
Internal Medicine, Baylor Scott & White Health, Temple/Texas A&M Health Science Center College of Medicine, Temple, TX 76508, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 7 April 2017 / Revised: 28 April 2017 / Accepted: 28 April 2017 / Published: 11 May 2017
(This article belongs to the Section Global Health)
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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. View Full-Text
Keywords: angiogenic; cardiotonic steroids; cell signaling; cytotrophoblast; preeclampsia; synthetic receptors angiogenic; cardiotonic steroids; cell signaling; cytotrophoblast; preeclampsia; synthetic receptors
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MDPI and ACS Style

Pantho, A.F.; Price, M.; Ashraf, A.Z.; Wajid, U.; Khansari, M.E.; Jahan, A.; Afroze, S.H.; Rhaman, M.M.; Johnson, C.R.; Kuehl, T.J.; Hossain, M.A.; Uddin, M.N. Synthetic Receptors Induce Anti Angiogenic and Stress Signaling on Human First Trimester Cytotrophoblast Cells. Int. J. Environ. Res. Public Health 2017, 14, 517.

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