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.

Study Design

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-β1 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-β1, production was significantly stimulated by the presence of nicotine. Vascular endothelial growth factor was undetectable.

Conclusion

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.

Key words: nicotine, placental growth factor (PlGF), preeclampsia, soluble fms-like tyrosine kinase 1 (sFlt1), soluble endoglin (sEng)