ELEVATED NONESTERIFIED FATTY-ACID CONCENTRATIONS IN SEVERE PREECLAMPSIA SHIFT THE ISOELECTRIC CHARACTERISTICS OF PLASMA-ALBUMIN

We previously hypothesized that the endothelial cell dysfunction obser ved in women with preeclampsia might be caused by an imbalance between circulating very low density lipoproteins and a cytoprotective pI 5.6 isoform of albumin, referred to as toxicity preventing albumin (TxPA) . An accurate simplified method was developed to quantify TxPA in smal l volumes of pregnancy plasma by gel electrofocusing. This assay revea led that circulating TxPA concentrations in women with severe preeclam psia were significantly reduced compared to those in normal pregnant w omen and women with benign transient hypertension of pregnancy. Nonest erified fatty acids (NEFA) and triglycerides were elevated in plasma f rom women with severe preeclampsia compared to those in plasma from th e two control groups. The inverse correlation between TxPA and NEFA va lues led us to analyze the NEFA bound to plasma albumin. Gas chromatog raphy and mass spectrometry demonstrated no qualitative differences in the specific fatty acids bound to plasma albumin in severe preeclampt ic and normal pregnant women. However, the quantity of NEFA bound to a lbumin was greater in preeclampsia plasma (2.5 mol NEFA/mol albumin) c ompared to that in normal pregnancy plasma (0.8 mol NEFA/mol albumin), accounting for the acidic pi shift observed in albumin from the forme r patients. Functional assays demonstrated that human very low density lipoprotein particles were toxic to human umbilical vein endothelial cells in vitro, but this toxicity was prevented by the addition of TxP A albumin to the culture medium.