270-POS

Abstract

Objectives In this study we tested the hypothesis that nicotine restores proangiogenic functions to endothelial cells pretreated with soluble fms-like tyrosine kinase 1 and/or soluble endoglin and that nicotine inhibits interleukin 6 (IL-6) productions which maternal serum stimulates. Methods Wound healing assay and tube formation assay were performed using human umbilical vein endothelial cells (HUVECs) treated with nicotine, and with various combinations of soluble fms-like tyrosine kinase 1, soluble endoglin, and nicotine. Enzyme-linked immunosorbent assay (ELISA) was performed to measure vascular endothelial growth factor, placental growth factor, and transforming growth factor- 1 concentrations in the conditioned media treated with nicotine. HUVECs were incubated with or without 0.5% serum from healthy pregnant women at term and treated with or without nicotine in the presence of 0.5% serum. Cell survival was determined by colorimetric assay. IL-6 concentration and nuclear transcription factor kappa B (NF-kB) activities were determined by ELISA-based method. Results Nicotine significantly facilitated endothelial migration and tube formation. By contrast, soluble fms-like tyrosine kinase 1 and/or soluble endoglin suppressed these endothelial functions. Nicotine restored these soluble fms-like tyrosine kinase 1 and/or soluble endoglin reduced endothelial functions. Placental growth factor, but not transforming growth factor-1, production was significantly stimulated by the presence of nicotine. Vascular endothelial growth factor was undetectable. IL-6 production by endothelial cells was significantly stimulated in the presence of maternal serum. Nicotine significantly preserved cell survival and suppressed IL-6 production from endothelial cells. Nicotine also significantly inhibited NF-kB activation in endothelial cells. Conclusions Our results suggest a possible mechanism for the protective effects of cigarette smoking against preeclampsia, thus proposing a therapeutic potential of nicotine or other nicotinic acetylcholine receptor agonists for preeclampsia. Disclosures K. Mimura: None. T. Tomimatsu: None. T. Kimura: None.