Maternal Plasma From Pregnant Women With Umbilical Placental Vascular Disease Does Not Affect Endothelial Cell mRNA Expression of Nitric Oxide Synthase

Objective: In placental vascular disease identified by umbilical artery Doppler study we have shown the existence of a factor in fetal plasma that causes activation of endothelial cells in culture with expression of cell adhesion molecules and nitric oxide synthase, apoptosis, and proinflammatory cytokine production. The present work was carried out to investigate a maternal origin for this factor active in the fetal circulation.

Methods: We collected maternal plasma from pregnant women with Doppler-defined umbilical placental vascular disease and examined its effect on endothelial cells in culture. Aliquots from a common culture of human umbilical vein endothelial cells (HUVEC) were incubated with maternal plasma from women with normal pregnancy (n = 23), umbilical placental vascular disease defined by abnormal umbilical artery Doppler (n = 30, with or without preeclampsia), and preeclampsia with normal umbilical artery Doppler (n = 14). The expression of mRNA for inducible and endothelial constitutive nitric oxide synthase (iNOS and ecNOS, respectively) was assessed by reverse transcriptase polymerase chain reaction.

Results: There was no significant increase in either the iNOS or the ecNOS mRNA expression by HUVEC cultured with maternal plasma from pregnancies with umbilical placental vascular disease compared with normal pregnancy (iNOS 1.49 ± 0.35 versus 1.38 ± 0.25; ecNOS 1.51 ± 0.35 versus 1.25 ± 0.27; P > .05). In the placental vascular disease group the results were similar for the presence or absence of maternal preeclampsia. In the samples from women with preeclampsia with normal umbilical Doppler, both iNOS and ecNOS mRNA expression (iNOS 1.42 ± 0.53; ecNOS 1.46 ± 0.39; P > .05) did not differ from normal.

Conclusion: Maternal plasma from pregnancies with umbilical placental vascular disease did not affect endothelial cell expression of nitric oxide synthase. This finding does not support a maternal origin for the factor demonstrated in fetal plasma. These results suggest separate pathogenic pathways for the endothelial cell activation seen in preeclampsia and fetal growth restriction associated with abnormal umbilical artery Doppler flow velocity waveforms. These findings are also consistent with the concept that the vascular pathology in the fetal placenta may be primary and that the uteroplacental circulation is reduced in response rather than acts as a constraint.