Preeclampsia and HELLP Syndrome: Impaired Mitochondrial Function in Umbilical Endothelial Cells

Abstract

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.

New therapeutic approaches to treating hypertension in pregnancy

“…The notion that energy provided by fatty acid metabolism is important for proper placental function supports the hypothesis that defects in the carnitine system and/or mitochondrial function might be relevant in the pathophysiology of preeclampsia [60,61]. A beneficial effect of L-carnitine supplementation on weight gain in premature neonates is not strongly supported at present, although such supplementation improved lipid profiles and serum carnitine levels [62].…”

Effects of 4-hydroxynonenal on vascular endothelial and smooth muscle cell redox signaling and function in health and disease

“…Activation of UPR effector pathways is clearly evidenced in the placentas of PE pregnancies [121], although no causative link has yet been made to suggest that ER stress occurs secondary to lipid peroxidation. Furthermore, ER stress remains to be assessed in the fetal vasculature, although markers of mitochondrial dysfunction are found in fetal endothelial cells [122] and are well documented in the placenta to co-inside with markers of oxidative stress [123].…”

Pre-eclampsia and offspring cardiovascular health: mechanistic insights from experimental studies

“…This independent effect of pre-eclampsia is not surprising, as fetal antioxidant capacity generally only increases in the last trimester after the increase in oxidative stress observed in early-onset pre-eclampsia [127,149]. Mitochondrial oxidative species may be particularly relevant to this fetal programming mechanism as, following pre-eclampsia, fetal-derived HUVECs have impaired mitochondrial function [150] associated with increased endothelial mitochondrial oxidative species generation.…”