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.
Illsinger
Sabine
S
Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany. illsinger.sabine@mh-hannover.de
Janzen
Nils
N
Sander
Stefanie
S
Schmidt
Karl-Heinz
KH
Bednarczyk
Jolanthe
J
Mallunat
Lisa
L
Bode
Julia
J
Hagebölling
Friederike
F
Hoy
Ludwig
L
Lücke
Thomas
T
Hass
Ralf
R
Das
Anibh M
AM
D000328:Adult; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004579:Electron Transport; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006019:Glycolysis; D017359:HELLP Syndrome / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000150:complications / Q000201:enzymology / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D010084:Oxidation-Reduction; D025221:Phosphofructokinases / Q000378:metabolism; D011225:Pre-Eclampsia / Q000209:etiology / Q000378:metabolism*; D011247:Pregnancy; D014471:Umbilical Veins
D005227:Fatty Acids; D009097:Multienzyme Complexes; C116917:acylcarnitine; D007770:L-Lactate Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase; D025221:Phosphofructokinases; D002331:Carnitine