Energy metabolism in umbilical endothelial cells from preterm and term neonates.

AIM: The aim of this study was to investigate the impact of gestational age on energy metabolism in human umbilical vein endothelial cells (HUVECs) of preterm and term neonates. METHODS: Activities of respiratory chain (RC) complexes I-V, citrate synthase (CS), overall mitochondrial fatty acid oxidation (FAO), carnitine palmitoyltransferase 2 (CPT2), glycolytic enzymes as well as energy-rich phosphates in HUVECs from uncomplicated term and preterm pregnancies were measured. Neonatal acylcarnitine profiles were analyzed postpartum. RESULTS: Activities of RC complexes II+III, IV, V, and CS were higher in HUVECs from immature pregnancies. Overall FAO did not change, whereas CPT2 activity was higher in term neonates. RC complexes II-V and CS correlated inversely to gestational age, as well as CPT2 activity within the term cohort. Phosphofructokinase activity increased with maturation; lactate dehydrogenase and hexokinase as well as energy-rich phosphates remained constant. In blood, long-chain acylcarnitines were higher in term neonates. CONCLUSIONS: Gestational age-dependent differences of energy-providing pathways in HUVECs were shown. Alterations of RC complexes with gestational age may be an adaptive process to cope with metabolic stress during birth; reduced oxidative phosphorylation and high glycolytic activity make HUVECs less susceptible to peripartum hypoxic damage. We hypothesize that HUVECs of premature neonates are metabolically maladapted to birth, which may be responsible for perinatal complications.

Preeclampsia and HELLP syndrome: impaired mitochondrial function in umbilical endothelial cells.

Preeclampsia (PE) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome have been linked to congenital fetal disorders of mitochondrial fatty acid oxidation (FAO). Different incidences may argue for the association of noncongenital alterations of mitochondrial energy metabolism with PE/HELLP syndrome. We studied human umbilical vein endothelial cells [HUVEC] as selected part of the feto-placental unit from uncomplicated (n = 46) and diseased (n = 27; 17 PE and 10 HELLP) pregnancies by measuring the overall FAO, carnitine palmitoyltransferase 2 (CPT2), respiratory chain (RC) complexes I-V, citratesynthase (CS), lactatedehydrogenase (LDH), hexokinase (HK), phosphofructokinase (PFK), and energy rich phosphates. Maternal and infantile acylcarnitines in blood were investigated post partum. Overall FAO, RC complexes II-V, and CS were significantly compromised in HUVEC from complicated pregnancies; impairment of complexes I + III was not significant. CPT2 and energy charges were unaffected. Lactatedehydrogenase and PFK from complicated pregnancies were upregulated, and HK remained constant. In blood, carnitine was elevated in diseased women and their children, acylcarnitines were higher in affected infants. Impaired mitochondrial function in HUVEC is associated with PE/HELLP syndrome and may be involved in the pathophysiology of these diseases.