Sera from preeclamptic patients contain factor(s) that stimulate prostacyclin production by human endothelial cells.

A relative decrease in endothelial cell prostacyclin production may be pivotal in the genesis of preeclampsia. We determined the effect of sera from preeclamptic women on prostacyclin production by monolayers of normal term human umbilical vein endothelial cells. Endothelial cells were incubated with media containing serum from patients with preeclampsia, non-hypertensive, gestational age-matched pregnant controls, or normal non-pregnant controls (N = 7, all groups). 6-Keto-prostaglandin F1 alpha, the stable metabolite of prostacyclin, was measured directly in the culture medium by radioimmunoassay. Treatment with preeclamptic sera, when associated with a statistically significant increase in prostacyclin metabolite production by endothelial cells. Thus, sera from women with preeclampsia stimulate rather than inhibit prostacyclin production by endothelial cells. We speculate that there is a factor in the sera of women with preeclampsia that functions to activate endothelial cells or which may play a role in the homeostatic mechanisms to balance reduced prostacyclin output in preeclampsia.     

Structural and functional changes in left ventricle during normotensive and preeclamptic pregnancy

Increased cardiac output in pregnancy is associated with cardiac remodeling and possible reduction in contractility, which may worsen in preeclampsia. Left ventricular (LV) geometry and function were compared between nonpregnant controls (n = 12) and normotensive (n = 44) and preeclamptic (n = 15) pregnant women using echocardiography. Load-independent comparisons of LV systolic function compared end-systolic stress (ESS) and rate-corrected velocity of circumferential fiber shortening (V(CFC)). Mean arterial pressures were 101 +/- 14 mmHg in preeclampsia, 76 +/- 6 mmHg in normotensive pregnancy, and 78 +/- 6 mmHg in controls (P < 0.005 vs. preeclampsia). LV mass increased during normotensive pregnancy (66 +/- 13 to 76 +/- 16 g/m(2); P < 0.05; controls, 65 +/- 10 g/m(2); P < 0.05) and was greater in preeclampsia (90 +/- 18 g/m(2); P < 0.05). In normotensive pregnancy, ESS decreased (59 +/- 9 to 52 +/- 11 g/cm(2); P < 0.05; controls, 66 +/- 14 g/cm(2); P < 0.005). ESS was greater in preeclampsia (60 +/- 14 g/cm(2); P < 0.05). In controls, there was an inverse relationship between ESS and V(CFC) (r = -0.78). The ESS-V(CFC) relationships in normotensive and preeclamptic pregnancy were unchanged from controls. We conclude that LV hypertrophy in normotensive and preeclamptic pregnancy matches changes in cardiac work, and LV contractility is preserved.     

Plasma protein carbonyls in nonpregnant, healthy pregnant and preeclamptic women

Increased reactive oxygen species (ROS) and lipid peroxidation may be implicated in the pathogenesis of preeclampsia by causing cell (membrane) damage and impaired endothelial function. Carbonyl derivatives of proteins, or protein carbonyls, may be sensitive biomarkers of ROS-mediated damage. The aim of the study was to compare levels of protein carbonyls in plasma of preeclamptic, healthy pregnant and healthy nonpregnant women. Plasma protein carbonyls were measured in 47 preeclamptic, 45 healthy pregnant and 22 healthy nonpregnant women by using a sensitive ELISA-method. ANOVA, the unpaired t-test and Pearson's correlation were used for statistical analysis. Preeclamptic women had significantly higher plasma protein carbonyl levels than healthy pregnant women (P < 0.0001). Healthy pregnant women showed significantly higher protein carbonyl levels (P < 0.001) as compared to nonpregnant controls. The higher levels of protein carbonyls as compared to nonpregnant controls suggest that increased oxygen free radical damage occurs in normal pregnancy and to a much higher extent in preeclampsia.     

Lipid peroxidation and active calcium transport in inside-out vesicles of red blood cells from preeclamptic women

We previously reported that in preeclampsia Ca-ATPase activity diminishes about 50% in red blood cells, myometrium and syncitiotrophoblast plasma membranes. In this work, we measured the active Ca++ uptake by inside-out vesicles of human red blood cells from preeclamptic and normotensive pregnant women. Active calcium uptake by the vesicles was diminished by 49+/-3% in the preeclamptic women as compared to the gestational controls ( 8.06 +/- 0.11 nmol Ca++/mg protein min, gestational controls; 4.08 +/- 0.1 nmol Ca++/mg protein min, preeclamptics). This lowered calcium uptake correlates well with the lowered Ca-ATPase activity found in the red blood cells ghosts of the preeclamptic women (17.05 +/- 0.96 nmol Pi/mg protein min, gestational controls; 8.85 +/- 0.45 nmol Pi/mg protein min, preeclamptics). The reduced calcium uptake and Ca-ATPase activity of the red cell membranes both appear to be associated with a high level of lipid peroxidation. Thus there is a diminution in the active transport of calcium in the red blood cells of preeclamptic women. If this also occurs in other cell types of the preclamptic women, it could result in an increase in their cytosolic calcium concentration which might be responsible, in part, for some of the symptoms of this disease.     

Plasma protein carbonyls in nonpregnant,healthy pregnant and preeclamptic women

Increased reactive oxygen species (ROS) and lipid peroxidation may be implicated in the pathogenesis of preeclampsia by causing cell (membrane) damage and impaired endothelial function. Carbonyl derivatives of proteins, or protein carbonyls, may be sensitive biomarkers of ROS-mediated damage. The aim of the study was to compare levels of protein carbonyls in plasma of preeclamptic, healthy pregnant and healthy nonpregnant women.

Plasma protein carbonyls were measured in 47 preeclamptic, 45 healthy pregnant and 22 healthy non-pregnant women by using a sensitive ELISA-method. ANOVA, the unpaired t-test and Pearson's correlation were used for statistical analysis.

Preeclamptic women had significantly higher plasma protein carbonyl levels than healthy pregnant women (P < 0.0001). Healthy pregnant women showed significantly higher protein carbonyl levels (P < 0.001) as compared to nonpregnant controls.

The higher levels of protein carbonyls as compared to nonpregnant controls suggest that increased oxygen free radical damage occurs in normal pregnancy and to a much higher extent in preeclampsia.     

Heart Rate Variability and Autonomic Modulations in Preeclampsia

BackgroundAlthough the exact pathophysiology of preeclampsia is not well understood, autonomic nervous system imbalance is suggested as one of the main factors.AimsTo investigate heart rate variability (HRV) and autonomic modulations in Sudanese pregnant women with preeclampsia.ResultsPatients with preeclampsia achieved significantly higher LF Norm [49.80 (16.25) vs. 44.55 (19.15), P = 0.044] and LnLF/HF [0.04 (0.68) vs. -0.28 (0.91), P = 0.023] readings, but lower HF Norm [49.08 (15.29) vs. 55.87 (19.56), P = 0.012], compared with healthy pregnant women. Although all other HRV measurements were higher in the patients with preeclampsia compared with the controls, only LnVLF [4.50 (1.19) vs. 4.01 (1.06), P = 0.017] and LnLF [4.01 (1.58) vs. 3.49 (1.23), P = 0.040] reached statistical significance.ConclusionThe study adds further evidence for the dominant cardiac sympathetic modulations on patients with preeclampsia, probably secondary to parasympathetic withdrawal in this group. However, the higher LnVLF and LnLF readings achieved by preeclamptic women compared with the controls are unexpected in the view that augmented sympathetic modulations usually depresses all HRV parameters including these two measures.     

Analysis of nitroso-proteomes in normotensive and severe preeclamptic human placentas

Nitric oxide (NO) plays a key role in placental biology, and placental dysfunction is the main pathogenesis pathway for preeclampsia, yet the direct placental targets of NO actions have not been determined. Covalent adduction of an NO moiety to cysteines, termed S-nitrosylation (SNO), is emerging as a key route by which NO can directly modulate protein functions. This study was conducted to analyze global S-nitroso (SNO)-proteins in human placentas and to determine if their levels differ in normotensive versus severe preeclamptic placentas. Although total nitrite/nitrate increased, total levels of SNO-proteins and nitrosylated forms of endothelial NO synthase and heat shock protein 90 were decreased by preeclampsia. We further compared normotensive and preeclamptic placental nitroso-proteomes (total SNO-protein profiles) by using a biotin and CyDye switch test combined with two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and identified SNO-proteins by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Numerous SNO-proteins were displayed as spots on 2D-DIGE gels. One hundred spots of interest were excised; 46 spots were identified, of which 8 spots were novel SNO-proteins; levels of 15 spots were increased, and 6 spots were decreased, and the rest were unchanged by preeclampsia. Pathway analysis suggested that placental SNO-proteins are involved in regulating various cellular functions including protein synthesis, cell movement and metabolism, cell signaling, and other functions. These data therefore show for the first time that SNO is a crucial mechanism by which NO directly regulates placental proteins linked to various biological pathways. The significantly altered placental nitroso-proteome in preeclampsia suggests that SNO plays a role in the placental pathophysiology in preeclampsia.     

Interleukin-6 concentrations in the placenta and blood in normal pregnancies and preeclampsia.

AIM: To evaluate whether IL-6 concentrations in the placenta and blood from women with preeclampsia differed from those in normal pregnancies. METHODS: This study involved 41 pregnant women carrying single fetuses. Of these pregnancies, 23 were normal pregnant and 18 were preeclamptic patients. The average gestational age at entry was 37-38 weeks of gestation. Blood was collected before the onset of labor. Serum was separated and stored at -20 degrees C. A tissue segment of the placenta was cut and chilled in liquid nitrogen immediately after delivery and stored at -80 degrees C. The frozen tissue was added to phosphate-buffered saline and fully homogenized. After centrifugation, the separated supernatant was stored at -80 degrees C. IL-6 levels in separated serum and IL-6 and total protein (TP) levels in separated supernatant were measured. The presence of IL-6 in the placenta was evaluated by immunohistochemistry in five preeclamptic and five normal pregnant patients. RESULTS: Neither IL-6/TP levels in the placenta nor IL-6 levels in blood differed significantly between the two groups. IL-6 immunostaining on trophoblastic cells in the placenta was weak in one and absent in four in normal pregnancies, and absent in all patients with preeclampsia. There was no strong immunostaining for IL-6 in preeclampsia by immunohistochemistry. CONCLUSIONS: Our findings suggest that IL-6 in the placenta and blood does not play a significant role in the induction of an immunologic imbalance, which may contribute to the etiological mechanism leading to preeclampsia.     

Plasminogen activator inhibitor-1 polymorphism in women with pre-eclampsia

We determined whether or not genetic variability in the promoter region of the gene encoding plasminogen activator inhibitor-1 (PAI1) contributes to individual differences in susceptibility to the development of preeclampsia. The study involved 133 preeclamptic and 115 healthy control pregnant women who were genotyped for a single-nucleotide insertion/deletion polymorphism (4G/5G) at position -675 in the PAI1 gene promoter. Furthermore, the frequencies of the alleles in the general middle-aged population are presented for comparison. Chi-square analysis was used to assess genotype and allele frequency differences between preeclamptic women and controls. A similar allelic distribution of PAI1 4G/5G polymorphism was observed in the two groups, with the frequency of the variant 4G allele being 50.4% in the preeclampsia group and 54.3% in the control group (p = 0.377; OR = 0.85, 95% CI = 0.60-1.22). Accordingly, the genotype distribution of the PAI1 4G/5G polymorphism in the preeclamptic and control groups was found to be similar (p = 0.68). Overall, this genotype data on fertile women is almost identical to that in the general middle-aged Finnish population. The 4G/5G polymorphism of the PAI1 gene promoter is unlikely to be a major genetic predisposing factor as regards preeclampsia in subjects from eastern Finland. These results are not suggestive of an important contribution of the PAI1 genotype on preeclampsia across populations.     

Oxidized transthyretin in amniotic fluid as an early marker of preeclampsia

Preeclampsia is a pregnancy-specific hypertensive syndrome and a major cause of maternal and fetal morbidity and mortality. At the present time, no reliable screening tests to identify women at risk are available. We have compared the amniotic fluids (AF) proteomic maps of five preeclamptic patients with those of five controls. The analysis was carried out by two-dimensional electrophoresis followed by peptide mapping and tandem mass spectrometric analysis. Besides the implementation of the previously published AF proteomic maps, our results show that transthyretin (TTR), the protein responsible for transporting both the thyroid hormone tyroxine and the retinol binding protein, is present in the AF of both preeclamptic and control women as a mixture of dimeric and post-translationally modified monomeric forms. Although the nature of these forms is similar in both groups, the preeclamptic women showed a significant increase in the amount of monomeric proteins with respect to the control group. Since the TTR monomeric forms are the results of different oxidizing reactions, we hypothesize that the higher oxidative stress in preeclampsia is the major destabilizing factor of the TTR functional dimeric form in the preeclamptic women.     

Impairment of endothelial function in women with a history of preeclampsia: an indicator of cardiovascular risk

Preeclampsia is a disorder of pregnancy diagnosed by gestational hypertension and proteinuria. Epidemiological evidence suggests that women who experience preeclampsia are at a greater risk of hypertension and heart disease later in life compared with women who had normal pregnancies. Our objective was to determine whether endothelial function is impaired in postpartum women with a history of preeclampsia in their first pregnancy. We measured forearm blood flow (FBF) by venous occlusion plethysmography in 50 healthy women: 16 with prior preeclampsia, 14 with a prior normotensive pregnancy, and 20 never pregnant controls. The postpartum women participated 6-12 mo after delivery. Heart rate (HR) and blood pressure (BP) were concurrently monitored on the contralateral arm. Hemodynamic variables were assessed at baseline and during a mental stress test known to elicit endothelium-dependent vasodilatation. We found that baseline FBF, HR, systolic BP, and diastolic BP did not significantly differ among the groups, whereas mean arterial pressure in the preeclamptic group was greater than that of the normal pregnancy group (P = 0.03). Stress-induced FBF (percent change over baseline) was reduced in the preeclamptic group compared with both the normal pregnancy and never pregnant groups (P = 0.06) and was significantly attenuated compared with women with prior normal pregnancies (91% vs. 147%, P = 0.006). These data demonstrate that women with a history of preeclampsia exhibit impaired endothelial function up to 1 yr postpartum. This observation may explain their increased risk for hypertension and cardiovascular disease.     

Lead Accumulation as Possible Risk Factor for Primary Open-Angle Glaucoma

The objective of this study was to investigate the relationship between preeclampsia and iodine levels and magnesium concentration in the blood of subjects in the northeast Anatolia region where iodine deficiency is common. Blood specimens were obtained from 24 preeclamptic and 16 healthy pregnant women. Iodine levels in blood were determined by the Foss method based on the Sandell–Kolthoff reaction. Serum protein-bound iodine (PBI) levels and magnesium concentration in maternal blood were lower in patients with severe preeclampsia compared to normal pregnant women (8.46?±?1.22 vs. 11.46?±?1.71 μg/dL, p?<?0.001, 1.63?±?0.05 vs. 1.86?±?0.05 mg/dL, p?<?0.001, respectively). Serum PBI levels and magnesium concentration in umbilical cord blood were higher in patients with severe preeclampsia than in normal pregnant women (8.84?±?1.9 vs. 7.33?±?1.07 μg/dL, p?<?0.05, 2.48?±?0.03 vs. 2.02?±?0.01 mg/dL, p?<?0.001, respectively). There was a positive correlation between the serum PBI levels in maternal blood and magnesium concentration in maternal blood in patients with severe preeclampsia (r?=?0.41, p?<?0.05). Thus, iodine may be one factor contributing to the pathophysiology of preeclampsia. Iodine supplementation may be effective therapy in preeclamptic in pregnant women.     

Role of Periodontal Bacteria,Viruses, and Placental mir155 in Chronic Periodontitis and Preeclampsia—A Genetic Microbiological Study

Previous studies assessed the involvement and impact of periodontal bacteria in preeclamptic women with chronic periodontitis. To explore further, the current study aimed to associate periodontal viruses and bacteria with mir155 levels in placental tissues of preeclamptic women with generalized chronic periodontitis. Four-hundred 45 pregnant women, 18–35 years of age, were selected and divided into four groups (controls, A, B, and C) where the Controls included 145 systemically and periodontally healthy pregnant women Group A-100 systemically healthy pregnant women with chronic periodontitis, Group B- 100 preeclamptic women with chronic periodontitis, Group C- 100 preeclamptic women without chronic periodontitis. Age, BMI, SES, and periodontal parameters such as PI, BOP, PPD, and CAL were noted. Periodontal pathogens such as Tf, Td, Pg, Pi, Fn, HSV, EBV, and HCMV were tested in subgingival plaque, placental tissues, and mir155. We observed that PI, BOP, PPD, CAL, Tf, and EBV were highly significant in Group B. We found a higher number of periodontal bacteria, viruses, and mir 155 in Group B showing a higher risk of preeclampsia. More genetic studies in this field are advised to ascertain the role of periodontopathogens and mir 155 in preeclampsia and periodontal inflammation. What is already known on this subject? Periodontal diseases pose an increased risk of developing preeclampsia and delivering preterm and/or low-birth-weight babies. What do the results of this study add? Periodontal variables such as PI, pocket depth, BOP, and clinical attachment levels, were found to be increased in the preeclamptic women with chronic periodontitis. The significant difference was seen in the relative fold expression of mir155 with higher gene expression of mir155 in groups B and A as compared to group C and controls. What are the implications of these findings for clinical practice and/or further research? In our study, mir155 correlation with the periodontal parameters and periodontal pathogens further strengthen the evidence of periodontal inflammation as a risk of preeclampsia in pregnant women especially when associated with chronic periodontitis. mir155 can be considered to be one of the genetic biomarkers and can be used as a diagnostic tool for the early detection of PE.     

Decreased fractional urinary calcium excretion and serum 1,25-dihydroxyvitamin D and IGF-I levels in preeclampsia

During preeclampsia several alterations of calcium metabolism have been described, the most common of them is hypocalciuria, which pathophysiology is still unclear. In order to assess the contribution of calciotropic hormones to urinary calcium excretion, a cross-sectional study was done including 26 preeclamptic Mexican women (PE group) and 26 normotensive control pregnant women (NT group). Total and fractional urinary calcium excretion were significantly lower (P<0.0001) in the PE group than in the NT group (82+/-7 versus 171+/-7 mg/24h and 0.62+/-0.38 versus 1.38+/-0.71%, respectively), without significant differences in creatinine clearance, urinary sodium excretion and phosphate tubular reabsorption. In addition, serum 1,25-(OH)(2)D and IGF-I levels were significantly (P<0.05) lower in the PE than in NT group (43+/-9 versus 50+/-9 pg/mL and 195+/-67 versus 293+/-105 ng/mL, respectively), without significant differences in serum PTH levels. In the NT group, association analysis showed that total and fractional urinary calcium excretions positively correlated with serum levels of 1,25-(OH)(2)D (P<0.01) and IGF-I (P<0.001). In the PE group, total urinary calcium excretion positively correlated only with serum 1,25-(OH)(2)D (P<0.05). In conclusion, the results obtained in this study confirm that PE is associated with hypocalciuria and suggest that 1,25-(OH)(2)D and/or IGF-I may be involved in the regulation of urinary calcium excretion.     

Two-dimensional immunoblot analysis of antigenic proteins of Spirometra plerocercoid recognized by human patient sera

Sparganosis is caused by invasion of Spirometra plerocercoid into various tissues/organs. Subcutaneous sparganosis can be diagnosed and treated by worm removal, while visceral/cerebral sparganosis is not easy to diagnose. The diagnosis depends largely on the detection of specific antibodies circulating in the patients' sera. Previous studies demonstrated that 31 and 36kDa proteins of the sparganum invoked specific and sensitive antibody responses, but also showed cross reactions with cysticercosis sera. We enriched protein fractions containing 31-36kDa through gel filtration and examined immune recognition pattern against the patient sera by 2-dimensional electrophoresis (2-DE) followed by immunoblotting. Serum samples from sparganosis patients recognized 8-10 protein spots of 31 and 36kDa with different isoelectric point (pI) values with variable combinations, in which four spots of 31kDa with pIs 3.4, 3.9, 4.0 and 4.1, and one 36kDa spot (pI 3.5) appeared to be specifically reactive. One 31kDa protein spot with pI 3.3 and two spots of 36kDa with pIs 3.3 and 3.5 reacted crossly with neurocysticercosis sera. Neither sera from patients with other parasitic infections nor those from healthy controls showed positive reaction. Two-DE/immunoblot analysis might be highly available in differential serodiagnosis of human sparganosis.     

An imbalance between prostacyclin and thromboxane in relation to cerebral blood flow in neonates with maternal preeclampsia.

OBJECTIVE: A disturbance of prostacyclin (PGI2) and thromboxane A2 (TXA2) balance has been reported in preeclampsia. However, little is known about the concentrations of these prostanoids in neonates born to preeclamptic pregnant women. The purpose of this study is to determine whether the PGI2 and TXA2 concentrations are altered and whether the prostanoid balance correlates to the cerebral blood flow in neonates born to preeclampsia. METHODS: Spontaneously voided urine samples were collected from 20 neonates of normotensive and 16 neonates of preeclamptic women during the first 24 h after birth. We measured by radioimmunoassay the concentrations of urinary 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and 11-dehydro-thromboxane B2 (11-dehydro-TXB2), respectively. Blood flow velocity in the middle cerebral artery was studied by pulsed Doppler ultrasonography in the neonates between 17 and 38 h after birth. RESULTS: There was no significant difference between the urinary 6-keto-PGF1alpha in the neonates of mothers with and without preeclampsia (median, 5.3 vs. 3.6 ng/mg of creatinine). In contrast, the urinary 11-dehydro-TXB2 and the ratio of 11-dehydro-TXB2 to 6-keto-PGF1alpha in the neonates of mothers with preeclampsia were significantly lower as compared with the neonates without preeclampsia, respectively (13.7 vs. 20.6 ng/mg of creatinine and 3.0 vs. 5.2, median). The resistance index in the middle cerebral artery was significantly reduced in the neonates with preeclampsia than without preeclampsia (0.67 +/- 0.01 vs. 0.74 +/- 0.02, mean +/- SEM). CONCLUSIONS: There was an association between maternal preeclampsia and the imbalance in the neonatal urinary excretion of PGI2 and TXA2 metabolites. This imbalance may contribute to the regulation of cerebral blood flow.     

Comparative Study of Serum Zinc, Copper, Manganese, and Iron in Preeclamptic Pregnant Women

Preeclampsia complicates 2–8 % of all pregnancies and it is one of the leading causes of maternal mortality and pre-term delivery in the world. Unfortunately, there is scarcity of document discussing the circulating level of several essential trace elements in preeclampsia patients in Bangladesh. The present study was designed to evaluate the serum concentration of four trace elements, namely zinc, copper, manganese, and iron, in preeclamptic pregnant women. The study was conducted as a case–control study with 50 preeclamptic pregnant women as cases and 58 normotensive pregnant women as controls. Obstetric, anthropometric, and clinical data were collected at routine obstetric visits. Serum trace elements were determined by flame atomic absorption spectroscopy. Independent sample t test and Pearson’s correlation test were done for the statistical analysis using the statistical software package SPSS, version 16.0 (SPSS Inc., Chicago, IL). We observed significant differences for gestational age, body mass index, and systolic and diastolic blood pressure between patient and control groups (p?<?0.05). Analysis of serum trace elements explored significantly lower level of all the four elements in preeclampsia patients in comparison to the control group (p?<?0.05). Pearson’s correlation analysis explored that the correlation between serum level of different trace elements was statistically insignificant (p?>?0.05) except the correlation between zinc and iron in preeclampsia patients (p?<?0.05). Establishment of inter-element relationship strongly supports that there was a disturbance in the element homeostasis in patient with preeclampsia. In conclusion, our study suggests that preeclampsia patients have considerably lower level of serum zinc, copper, manganese, and iron compared to the healthy pregnant women.     

An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia

Preeclampsia is a common pregnancy complication that is an important cause of preterm birth and fetal growth restriction. Because there is no diagnostic test yet available for preeclampsia, we used a proteomic approach to identify novel serum/plasma biomarkers for this condition. We conducted case control studies comparing nulliparous women who developed preeclampsia at 36-38 weeks of gestation with healthy nulliparous women matched by gestational age at sampling. Serum/plasma was depleted of six abundant proteins and analyzed by two-dimensional gel electrophoresis (n = 12 per group) and difference gel electrophoresis (n = 12 per group). Differences in abundance of protein spots were detected by univariate and multivariate statistical analyses. Proteins were identified by mass spectrometry and expression of selected proteins was validated by immunoblotting. Proteins whose concentrations were selectively associated with preeclampsia included apolipoprotein E (apoE), apoC-II, complement factor C3c, fibrinogen, transthyretin, and complement factor H-related protein 2. An increase in a deglycosylated isoform of apoE3 and concomitantly decreased amounts of one apoE3 glycoisoform were identified in preeclamptic plasma and confirmed by immunoblotting. Altered production of these preeclampsia-related apoE3 isoforms might impair reverse cholesterol transport, contributing to arterial damage. These findings point to a novel mechanistic link between preeclampsia and subsequent cardiovascular disease.