Abstract

Fetal growth restriction associated with hypertensive disorders of pregnancy (FGR-HDP) is a prevalent pathology with a higher risk of perinatal morbimortality. In this condition, placental insufficiency and endothelial dysfunction serve key roles. The present prospective cohort study monitored 11 patients with an FGR-HDP and 15 with full-term normotensive pregnancies and studied post-natal intracellular calcium concentration ([Ca2+](i)) signals in human umbilical vein endothelial cells (HUVECs). Small fetuses with placental insufficiency were identified using fetal biometry with Doppler velocimetry. Mean gestational age and birth weight were 31.8 +/- 4.1 weeks and 1,260 +/- 646 g for FGR-HDP and 39.2 +/- 0.8 weeks and 3,320 +/- 336 g for normal births, respectively. Abnormal umbilical artery Doppler waveforms were found in 64% of neonates with FGR-HDP. A significant percentage (86%) of FGR newborns were admitted to the neonatal intensive care unit at Gustavo Fricke hospital, Vi & ntilde;a del Mar, Chile, with one case of death after birth. [Ca2+](i) signals were measured by microfluorimetry in Fluo-3-loaded HUVECs from primary cultures. Altered [Ca2+](i) signals were observed in HUVECs from FGR-HDP, where the sustained phase of ATP-induced [Ca2+](i) responses was significantly reduced compared with the normotensive group. Also, the [Ca2+](i) signals induced with 10 mM Ca2+ after depletion of internal Ca2+ stores were significantly higher. The present study provides a better comprehension of the role of altered cytosolic Ca2+ dynamics in endothelial dysfunction and an in vitro model to assess novel therapeutic approaches for decreasing or preventing complications in FGR-HDP.