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.

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).

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.

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.