title: Nicotine promotes vascular endothelial growth factor secretion by human trophoblast cells under hypoxic conditions and improves the proliferation and tube formation capacity of human umbilical endothelial cells.
abstract: Pre-eclampsia, characterized as defective uteroplacental vascularization, remains the major cause of maternal and fetal mortality and morbidity. Previous epidemiological studies demonstrated that cigarette smoking reduced the risk of pre-eclampsia. However, the molecular mechanism remains elusive. In the present study, it is demonstrated that a low dose of nicotine decreased soluble vascular endothelial growth factor receptor 1 (sFlt1) secretion in human trophoblast cells under hypoxic conditions. Nicotine was then observed to promote vascular endothelial growth factor (VEGF) secretion by reducing sFlt1 secretion and increasing VEGF mRNA transcription. Further data showed that nicotine enhanced hypoxia-mediated hypoxia-inducible factor-1α (HIF-1α) expression and HIF-1α small interfering RNA abrogated nicotine-induced VEGF secretion, indicating that HIF-1α may be responsible for nicotine-mediated VEGF transcription under hypoxic conditions. Moreover, conditioned medium from human trophoblast cells treated with nicotine under hypoxic conditions promoted the proliferation and tube formation capacity of human umbilical endothelial cells (HUVEC) by promoting VEGF secretion. These findings indicate that nicotine may promote VEGF secretion in human trophoblast cells under hypoxic conditions by reducing sFlt1 secretion and up-regulating VEGF transcription and improve the proliferation and tube formation of HUVEC cells, which may contribute to elucidate the protective effect of cigarette smoking against pre-eclampsia.
authors.affiliation: Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital and Institute of Obstetrics and Gynecology, Fudan University, Shanghai, China. Electronic address: zhaohongbo01@sina.com.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Institute of Life Sciences, Chongqing Medical Universtiy, Chongqing, China.
authors.forename: Lanxiang
authors.initials: L
authors.lastname: Wu
authors.affiliation: Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital and Institute of Obstetrics and Gynecology, Fudan University, Shanghai, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital and Institute of Obstetrics and Gynecology, Fudan University, Shanghai, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital and Institute of Obstetrics and Gynecology, Fudan University, Shanghai, China.
authors.forename: Ruixia
authors.initials: R
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital and Institute of Obstetrics and Gynecology, Fudan University, Shanghai, China.
authors.forename: Jiabing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital and Institute of Obstetrics and Gynecology, Fudan University, Shanghai, China.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital and Institute of Obstetrics and Gynecology, Fudan University, Shanghai, China; Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, 200032, China. Electronic address: xucongjian@gmail.com.
authors.forename: Congjian
authors.initials: C
authors.lastname: Xu
mesh_terms: D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D009538:Nicotine; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Nicotine; VEGF; pre-eclampsia; trophoblast cells