Nicotine restores endothelial dysfunction caused by excess sFlt1 and sEng in an in vitro model of preeclamptic vascular endothelium: a possible therapeutic role of nicotinic acetylcholine receptor (nAChR) agonists for preeclampsia.
OBJECTIVE
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.


METHODS
Wound healing assay and tube formation assay were performed using human umbilical vein endothelial cells treated with nicotine (10(-9) to 10(-6) M), and with various combinations of soluble fms-like tyrosine kinase 1 (100 ng/mL), soluble endoglin (100 ng/mL), and nicotine (10(-7) M). Enzyme-linked immunosorbent assay was performed to measure vascular endothelial growth factor, placental growth factor, and transforming growth factor-beta1 concentrations in the conditioned media treated with nicotine (10(-9) to 10(-6) M).


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-beta1, production was significantly stimulated by the presence of nicotine. Vascular endothelial growth factor was undetectable.


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.
Mimura
Kazuya
K
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan.
Tomimatsu
Takuji
T
Sharentuya
Namuxila
N
Tskitishvili
Ekaterine
E
Kinugasa-Taniguchi
Yukiko
Y
Kanagawa
Takeshi
T
Kimura
Tadashi
T
D015703:Antigens, CD / Q000502:physiology*; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000503:physiopathology*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000627:therapeutic use; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D018722:Nicotinic Agonists; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D009538:Nicotine; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1