Ca²⁺ signals in human umbilical endothelial cells derived from pregnancy with fetal growth restriction associated with hypertensive disorder

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, Viña 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.