Authors: Kwon, Ja-Young¹; Bai, Sang-Wook¹; Kwon, Young-Guen²; Kim, Se-Hoon³; Kim, Chul Hoon⁴; Kang, Moung Hwa¹; Linton, John A.⁵; Park, Yong-Won¹

Source: Acta Obstetricia et Gynecologica Scandinavica, Volume 89, Number 4, April 2010 , pp. 565-571(7)

Publisher: Informa Healthcare

Abstract:

<title>Abstract</title>

Objectives. To evaluate the effect of nicotine on the production of soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) in human umbilical vein endothelial cells (HUVECs) and trophoblast cells, and to assess the involvement of alpha 7 nicotinic acetylcholine receptor (αα7 nAChR) in this process. Methods. Commercially available full-term placental trophoblasts and HUVECs derived from the umbilical cord of a normal pregnancy were used. The expression of αα7 nAChR was assessed by immunostaining, RT-PCR, and western blotting. The expression of sFlt-1 and sEng protein in the cell media after 6 and 24 hours of treatment with nicotine was evaluated using a commercially available ELISA. To determine the involvement of αα7 nAChR in the nicotinic effect, cells were treated with the αα7 nAChR antagonist αα-bungarotoxin (αα-BGT) prior to the nicotine exposure. Levels of significance were determined using the Student's t-test and one-way ANOVA, and a p-value <  0.05 was considered significant. Main outcome measures. The levels of sFlt-1 and sEng protein were evaluated before and after the nicotine treatment with or without αα-BGT pre-treatment. Results. In trophoblast cells, a significant reduction of sFlt-1 and sEng protein was observed after 24 hours of nicotine treatment as compared to the untreated group (p == 0.002, 0.000). In HUVECs, nicotine only had a suppressive effect on the expression of sEng at 6 hours (p == 0.03); there was no effect on sFlt-1 expression. However, pre-treatment with αα-BGT did not reverse the nicotine-induced suppressive effect on the expression of sFlt-1 and sEng in trophoblasts and HUVECs. Conclusions. Nicotine reduced the production of sFlt-1 and sEng in trophoblasts and sEng in HUVECs. This effect was not mediated by αα7 nAChR.

Keywords: Nicotine; soluble fms-like tyrosine kinase-1; soluble endoglin; trophoblasts; human umbilical vein endothelial cells; alpha 7 nicotinic acetylcholine receptor; hypertension in pregnancy

Document Type: Research article

DOI: http://dx.doi.org/10.3109/00016341003692253

Affiliations: 1: 1Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Korea 2: 2Department of Biochemistry, Yonsei University, Seoul, Korea 3: 3Department of Pathology, Yonsei University College of Medicine, Seoul, Korea 4: 4Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea 5: 5Department of Family Medicine, Yonsei University College of Medicine, Seoul, Korea

Publication date: 2010-04-01

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