A potential role for free fatty acids in the pathogenesis  of preeclampsia.
OBJECTIVE
Pregnant women with the vascular complication of preeclampsia show altered lipid metabolism characterized by elevated circulating triglycerides and nonesterified free fatty acids. We have compared the effect of maternal plasma from women with and without preeclampsia on cultured vascular endothelial cells and determined whether these plasma-induced changes were reproduced with free fatty acid solutions of palmitic, oleic and linoleic acid, representative of circulating levels reported in preeclampsia.


METHODS
Lipid accumulation was quantified by oil-red O staining, apoptosis by terminal dUTP nick-end labelling (TUNEL) and the measurement of mitochondrial redox capacity, and membrane potential recorded using MTT reduction and JC-1 accumulation for human umbilical vein endothelial cells (HUVECs) exposed to plasma and free fatty acids.


RESULTS
Lipid droplet accumulation was significantly increased in cultured HUVECs conditioned with maternal plasma from pregnancies with preeclampsia compared with normal uncomplicated controls. This increase was replicated following exposure to free fatty acids at the combined concentrations defined in preeclampsia. Plasma from these women also caused a significant decrease in mitochondrial dehydrogenase activity, a marked reduction in mitochondrial membrane potential and an increase in apoptosis compared with normal pregnancy. Again these effects were reproduced using free fatty acids in combination at the levels previously associated with preeclampsia.


CONCLUSIONS
These findings support the concept of a circulating pathogenic factor for preeclampsia and highlight the possibility that this factor is not a single compound but perhaps the combined elevation of the free fatty acids palmitic, oleic and linoleic acid in the maternal circulation.
Robinson
Nicola J
NJ
Maternal and Fetal Health Research Group, School of Clinical and Laboratory Sciences, The University of Manchester, St Mary's Hospital, Manchester, UK.
Minchell
Laura J
LJ
Myers
Jenny E
JE
Hubel
Carl A
CA
Crocker
Ian P
IP
D017209:Apoptosis / Q000187:drug effects; D016022:Case-Control Studies; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005230:Fatty Acids, Nonesterified / Q000097:blood* / Q000494:pharmacology; D005260:Female; D006801:Humans; D019787:Linoleic Acid / Q000097:blood / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019301:Oleic Acid / Q000097:blood / Q000494:pharmacology; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000097:blood / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000097:blood* / Q000209:etiology*; D011247:Pregnancy
D005230:Fatty Acids, Nonesterified; D019301:Oleic Acid; D019308:Palmitic Acid; D019787:Linoleic Acid