Jl. Vigne et al., ELEVATED NONESTERIFIED FATTY-ACID CONCENTRATIONS IN SEVERE PREECLAMPSIA SHIFT THE ISOELECTRIC CHARACTERISTICS OF PLASMA-ALBUMIN, The Journal of clinical endocrinology and metabolism, 82(11), 1997, pp. 3786-3792
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.