Placental angiogenesis markers sFlt-1 and PlGF: response to cigarette smoke.

Excess soluble vascular endothelial growth factor receptor, fms-like tyrosine kinase-1 (sFlt-1), and reduced placental growth factor (PlGF) mediate the genesis of preeclampsia. Cigarette smoking reduces the risk of preeclampsia. We hypothesized that placental secretion of sFlt-1 and PlGF was affected by exposure to cigarette smoke extract. Term placental villous explants were cultured with cigarette smoke extract. Media were analyzed for sFlt-1 and PlGF. Apoptosis was measured by TUNEL staining. Results are reported as sFlt-1 or PlGF picogram/milliliter/milligram wet weight of explant. Exposure to cigarette smoke extract reduced secretion of sFlt-1 in a dose-dependent manner. There was no difference in apoptosis. In contrast with sFlt-1, PlGF did not decline when incubated with cigarette smoke extract. Exposure of placental villous explants to cigarette smoke extract results in a proangiogenic state with reduced sFlt-1 and relative abundance of PlGF. This is the reverse of changes that are seen in preeclampsia and may explain the reduction of preeclampsia in smokers.