Decreased Level of Cord Blood Circulating Endothelial Colony–Forming Cells in Preeclampsia

Abstract

Preeclampsia is a pregnancy-related disorder associated with increased cardiovascular risk for the offspring. Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. However, the effect of preeclampsia on fetal levels of ECFCs is largely unknown. In this study, we sought to determine whether cord blood ECFC abundance and function are altered in preeclampsia. We conducted a prospective cohort study that included women with normal (n=35) and preeclamptic (n=15) pregnancies. We measured ECFC levels in the umbilical cord blood of neonates and characterized ECFC phenotype, cloning-forming ability, proliferation and migration towards VEGF-A and FGF-2, in vitro formation of capillary-like structures, and in vivo vasculogenic ability in immunodeficient mice. We found that the level of cord blood ECFCs was statistically lower in preeclampsia than in control pregnancies (P = .04), a reduction that was independent of other obstetric factors. In addition, cord blood ECFCs from preeclamptic pregnancies required more time to emerge in culture than control ECFCs. However, once derived in culture, ECFC function was deemed normal and highly similar between preeclampsia and control, including the ability to form vascular networks in vivo. This study demonstrates that preeclampsia affects ECFC abundance in neonates. A reduced level of ECFCs during preeclamptic pregnancies may contribute to an increased risk of developing future cardiovascular events.

Endothelial cell dysfunction and preeclampsia

“…7 This finding was consistent after adjustment of most obstetric factors, suggesting that level of ECFCs was an independent factor in preeclampsia. 7 Moreover, recent studies have shown many important confounding factors on circulating levels of ECFCs, including body mass index and gestational age. 8 Furthermore, Yoder and colleagues 9 demonstrated that early endothelial progenitor cells that generate endothelial cell colony-forming units are hematopoietic in origin, fail to form perfused vessels in vivo, and are clonally distinct from ECFCs; thus, in addition to variations in the number of AC133þ/KDRþ/CD34 þ endothelial progenitor cells, which are distinguished from ECFCs, it remains unclear whether preeclampsia altered baseline levels in the peripheral blood ECFCs.…”

“…By contrast, the ECFC level in preeclampsia was statistically lower than in the control, with a median abundance of 1 colony per 10 mL of cord blood and a 25 th to 75 th interquartile range of 0 to 4 colonies per 10 mL of cord blood. 7 In addition, a significant portion of the women with preeclampsia in their study had no measurable ECFCs. 7 This finding was consistent after adjustment of most obstetric factors, suggesting that level of ECFCs was an independent factor in preeclampsia.…”

“…7 In addition, a significant portion of the women with preeclampsia in their study had no measurable ECFCs. 7 This finding was consistent after adjustment of most obstetric factors, suggesting that level of ECFCs was an independent factor in preeclampsia. 7 Moreover, recent studies have shown many important confounding factors on circulating levels of ECFCs, including body mass index and gestational age.…”

“…ECFCs are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. 7 It is hard to believe that the absolute number of ECFCs in the peripheral blood of pregnant women with preeclampsia is increased compared with that of women without preeclampsia. A recent study from Muñoz-Hernandez and colleagues 7 did not find any statistically significant difference of phenotypic and functional characteristics of cord blood ECFCs between pregnant women with and without preeclampsia.…”

Impaired Pulmonary Vascular Development in Bronchopulmonary Dysplasia

“…VEGF-NO signaling is impaired in circulating ECFCs isolated from the cord blood of preterm infants [91]. Recently ECFCs were shown to be decreased in cord blood of mothers with preeclampsia suggesting that impaired progenitor cell-mediated vasculogenesis is a mechanism through which the infant is affected by this maternal complication of pregnancy [92, 93]. ECFCs may also contribute to development of the placental vasculature and maternal vascular underperfusion (MVU) in the placenta is associated with BPD risk [94].…”