Is the atherosclerotic phenotype of preeclamptic placentas due to altered lipoprotein concentrations and placental lipoprotein receptors? Role of a small-for-gestational-age phenotype

Atherosis of spiral arteries in uteroplacental beds from preeclamptic women resemble those of atherosclerosis, characterized by increased plasma lipids and lipoproteins. We hypothesized that: 1) lipoprotein receptors/transporters in the placenta would be upregulated in preeclampsia, associated with increased maternal and fetal lipoprotein concentrations; and 2) expression of these would be reduced in preeclamptic placentae from women delivering small-for-gestational-age (SGA) infants. Placental biopsies and maternal and umbilical serum samples were taken from 27 normotensive and 24 preeclamptic women. Maternal/umbilical cord serum LDL, HDL, total cholesterol, and triglycerides were measured. Placental mRNA expression of lipoprotein receptors/transporters were quantified using quantitative RT-PCR. Protein localization/expression of LDL receptor-related protein 1 (LRP-1) in the preeclamptic placentae with/without SGA was measured by immunohistochemistry. Placental mRNA expression of all genes except paraoxonase-1 (PON-1), microsomal triglyceride transfer protein (MTTP), and protein disulfide isomerase family A member 2 (PDIA2) were observed. No differences for any lipoprotein receptors/transporters were found between groups; however, in the preeclamptic group placental LRP-1 expression was lower in SGA delivering mothers (n = 7; P = 0.036). LRP-1 protein was localized around fetal vessels and Hofbauer cells. This is the first detailed study of maternal/fetal lipoprotein concentrations and placental lipoprotein receptor mRNA expression in normotensive and preeclamptic pregnancies. These findings do not support a role of altered lipid metabolism in preeclampsia, but may be involved in fetal growth.     

Sex Differences in Lung Gas Volumes After Lipopolysaccharide-Induced Chorioamnionitis in Fetal Sheep

BackgroundPreterm female infants have a survival advantage and enhanced lung development, which is an important determinant of preterm survival.ObjectiveGiven the modulation of lung development by fetal exposure to infection/inflammation, we hypothesized that female fetuses have enhanced lung maturational responses to chorioamnionitis compared with male fetuses.MethodsTime-pregnant ewes received intra-amniotic injections with saline (n = 60) or lipopolysaccharide (LPS) at 2 days (n = 30) or 7 days (n = 45) before surgical delivery at 123 to 125 days of gestation (term: ∼147 days). We assessed inflammatory responses in bronchoalveolar lavage fluid and cord blood, lung maturation with pressure-volume curves, and lung structure.ResultsLung gas volume showed differences between the sexes after 2 days LPS (male 4.6 [1.2] mL/kg, female 7.7 [4.4] mL/kg; P = 0.02) and 7 days LPS (male 20.5 [9.3] mL/kg, female 27.0 [7.0] mL/kg; P = 0.01). The control group was not different by sex (male 8.0 [3.6] mL/kg, female 8.9 [3.9] mL/kg; P > 0.05). No difference in lung structure and in pulmonary and systemic inflammatory response was evident by sex.ConclusionPreterm female sheep fetuses had increased lung gas volumes after exposure to LPS, without any detectable differences in fetal inflammatory responses.     

Increased maternal and fetal cholesterol efflux capacity and placental CYP27A1 expression in preeclampsia

Preeclampsia is a pregnancy-specific condition that leads to increased cardiovascular risk in later life. A decrease in cholesterol efflux capacity is linked to CVD. We hypothesized that in preeclampsia there would be a disruption of maternal/fetal plasma to efflux cholesterol, as well as differences in the concentrations of both placental sterol 27-hydroxylase (CYP27A1) and apoA1 binding protein (AIBP). Total, HDL-, and ABCA1-mediated cholesterol effluxes were performed with maternal and fetal plasma from women with preeclampsia and normotensive controls (both n = 17). apoA1 and apoE were quantified by chemiluminescence, and 27-hydroxycholesterol (27-OHC) by GC-MS. Immunohistochemistry was used to determine placental expression/localization of CYP27A1, AIBP, apoA1, apoE, and SRB1. Maternal and fetal total and HDL-mediated cholesterol efflux capacities were increased in preeclampsia (by 10–20%), but ABCA1-mediated efflux was decreased (by 20–35%; P < 0.05). Maternal and fetal apoE concentrations were higher in preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples (P< 0.05). Placental protein expression of both CYP27A1 and AIBP were localized around fetal vessels and significantly increased in preeclampsia (P = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia (P < 0.05). Increased HDL-mediated cholesterol efflux capacity and placental CYP27A1/27-OHC could be a rescue mechanism in preeclampsia, to remove cholesterol from cells to limit lipid peroxidation and increase placental angiogenesis.     

Glycosylated Fibronectin and Inhibin are Lower and Anti-Müllerian Hormone is Higher in Umbilical Cord Blood when Mothers have Preeclampsia

Objective: Preeclampsia is a common disorder of pregnancy, causing significant morbidity and mortality for mothers and infants. Several molecules, including glycosylated fibronectin (GlyFn), the inhibin-related proteins, anti-müllerian hormone (AMH), and the insulin-like growth factor axis, are altered in maternal plasma in the setting of preeclampsia; however, these molecules have not been previously measured in cord blood of infants born to mothers with preeclampsia, which may represent changes in fetal physiology. We evaluated potential biomarkers of preeclampsia in umbilical cord blood to fill the gap in knowledge.Methods: This is a case-control study of 196 neonates born at a tertiary teaching hospital in Boston from 2010–2017. Forty-nine neonates born to mothers with preeclampsia were matched 1:3 by gestational age, sex, and birth weight z-score with 147 controls. Eleven analytes were measured in cord blood by enzyme-linked immunosorbent assay. Binary logistic regression analyses were performed to evaluate associations between preeclampsia and analytes.Results: Mean cord blood levels of GlyFn and total inhibin were significantly lower in neonates born to mothers with preeclampsia compared to controls, and AMH levels were significantly higher in males born to mothers with preeclampsia than male controls. Associations remained significant after controlling for maternal and neonatal characteristics.Conclusion: Cord blood levels of GlyFn and inhibin are decreased and AMH (male) levels are increased in infants of preeclamptic mothers, which is opposite the pattern these biomarkers show in serum of mothers with preeclampsia. These molecules may be important in the pathophysiology and long-term effects of preeclampsia on the developing fetus.Abbreviations: AMH = anti-müllerian hormone; ELISA = enzyme-linked immunosorbent assay; GlyFn = glycosylated fibronectin; IGF = insulin-like growth factor; IGFBP5 = insulin-like growth factor binding protein 5; LOD = limit of detection; PAPP-A = pregnancy-associated plasma protein A; PAPP-A2 = pregnancy-associated plasma protein A2     

Increased expression of high mobility group box 1 (HMGB1) in the cytoplasm of placental syncytiotrophoblast from preeclamptic placentae

BackgroundPreeclampsia is a pregnancy-specific disorder characterised by an inappropriate maternal inflammatory response during pregnancy. High mobility group box 1 (HMGB1) was originally characterised as a nuclear protein but when released into the extracellular environment following necrotic cell death, it is proinflammatory. HMGB1 is expressed in the syncytiotrophoblast of human placenta. Higher levels of uric acid are reported in preeclampsia. The aim of this study was to investigate whether the expression of HMGB1differed between early onset and late onset preeclampsia or severe and mild preeclampsia and whether its expression correlated with the levels of uric acid.Methods74 preeclamptic placentae and 110 normotensive placentae were included in this study. The levels of uric acid in women with preeclampsia were measured. The expression of HMGB1 in preeclamptic placentae or in first trimester and term placentae that had been treated with uric acid was measured.ResultsHMGB1 was expressed predominantly in the syncytiotrophoblast of the placenta and the expression of HMGB1 in the cytoplasm of the syncytiotrophoblast was significantly increased in both severe preeclampsia and early onset preeclampsia compared to normotensive pregnancies. The circulating levels of uric acid were significantly increased in preeclampsia and correlated with the expression of HMGB1. Increased levels of HMGB1 were significantly correlated with the severity and the time of onset of preeclampsia, but pathologic levels of uric acid did not increase the expression of HMGB1.ConclusionOur data provides a better understanding of the function of HMGB1, a danger molecule in the pathogenesis of preeclampsia.     

Does fetal sex affect pregnancy outcome?

Background: In maternal fetal medicine, gender differences in outcome are often observed.Objective: This article reviews the fetal sex-dependent differences found in many aspects of pregnancy, from conception through birth.Methods: The MEDLINE, EMBASE, and Current Contents databases were searched, for the years 1985 to 2006, using the following Medical Subject Headings and text words: fetal gender, finale, female, sex ratio at birth, pregnancy outcome, preterm birth, and stillbirth. The search was not limited by language. In addition, the bibliographies of known relevant articles were examined to capture any reports not already identified in the electronic search. All reports that provided information on gender differences in pregnancy outcome were included for review.Results: An extremely high male-to-female ratio was found in fetuses born after very short-duration pregnancy; this level declined around the 20th week and stabilized at term. In the absence of manipulation, both the sex ratio at birth and the population sex ratio have been found to remain consistent. A higher incidence of preterm birth and premature preterm rupture of membranes has been observed in different populations among mothers of male newborns compared with mothers of females. It has been speculated that this higher incidence may be linked to the relatively greater weight at lower gestational age of male newborns versus females. Women carrying male fetuses had higher rates of gestational diabetes mellitus, fetal macrosomia, failure to progress during the first and second stages of labor, cord prolapse, nuchal cord, and true umbilical cord knots. Cesarean sections were also more frequently found among male neonates compared with females.Conclusions: Male sex is an independent risk factor for adverse pregnancy outcome. Evidence suggests that females have an advantage over males, with a better outcome in the perinatal period, particularly after preterm birth.Key words: fetal gender, male, female, sex ratio of birth, perinatal outcome.     

Changes in placental dipeptidyl peptidase IV in preeclampsia with intrauterine growth restriction.

The purpose of this study was to examine alterations in placental expression of dipeptidyl peptidase IV (DPPIV). The localization of DPPIV was compared in control and preeclamptic placentas. Enzyme activity, mRNA, and protein expression were also measured. In term placentas, DPPIV was expressed preferentially in the fetal vascular endothelial cells within stem villi and only weakly in the villous stromal cells. DPPIV activity in control placentas showed no remarkable changes throughout gestation. Levels of activity in samples from normotensive control cases and women having preeclampsia with or without intrauterine growth restriction were 11.8 +/- 2.1, 13.4 +/- 1.1, and 15.3 +/- 0.62 pmol pNA/min/mg protein, respectively. The preeclamptic placentas with intrauterine growth restriction thus showed significantly higher levels of activity than the controls (p < 0.05). We propose that placental DPPIV influences fetal metabolism via the degradation of fetoplacental circulating bioactive peptides, including incretins, resulting in the regulation of fetal growth.     

Screening Preeclamptic Cord Plasma for Proteins Associated with Decreased Breast Cancer Susceptibility

Preeclampsia, a complication of pregnancy characterized by hypertension and proteinuria, has been found to reduce the subsequent risk for breast cancer in female offspring. As this pro- tective effect could be due to exposure to preeclampsia-specific proteins during intrauterine life, the proteomic profiles of umbilical cord blood plasma between preeclamptic and normotensive pregnancies were compared. Umbilical cord plasma samples, depleted of 14 abundant proteins, were subjected to proteomic analysis using the quantitative method of nanoACQUITY ultra performance liquid chromatography-mass spectrometry with elevated energy mode of acquisitionE （NanoUPLC-MSE）. Sixty-nine differentially expressed proteins were identified, of which 15 and 6 proteins were only detected in preeclamptic and normotensive pregnancies, respectively.Additionally, expression of 8 proteins （gelsolin, complement C5, keratin type I cytoskeletal 10, pigment epithelium-derived factor, complement factor B, complement component C7, hemoglobin subunit gamma-2 and alpha-fetoprotein） were up-regulated in preeclampsia with a fold change of 1〉 2.0 when compared to normotensive pregnancies. The identification of alpha-fetoprotein in pre- eclamptic umbilical cord blood plasma supported the validity of this screen as alpha-fetoprotein has anti-estrogenic properties and has previously been linked to preeclampsia as well as a reduced breast cancer risk. The findings of this pilot study may provide new insights into the mechanistic link between preeclampsia and potentially reduced breast cancer susceptibility in adult life.     

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.     

Maternal Cadmium Levels During Pregnancy and the Relationship with Preeclampsia and Fetal Biometric Parameters

Preeclampsia, which is caused by multiple factors, still remains one of the most serious complications of pregnancy. This study was designed to determine cadmium levels in women with preeclampsia compared to those of normotensive women. In this case-control study, maternal blood, umbilical cord blood, and placental cadmium levels were measured by an inductively coupled plasma mass spectrometry system in 51 women presenting consecutively with preeclampsia and 51 normotensive pregnant women. Groups were matched for maternal age, parity, and gestational age. Birth outcomes were recorded, such as gestational age at delivery, birth weight, and Apgar score. Median (interquartile range [IQR]) blood cadmium concentration was 1.21 μg/L (0.76–1.84 μg/L) and 1.09 μg/L (0.72–1.31 μg/L) in women with preeclampsia and normotensive, respectively; values for placental cadmium levels of women with preeclampsia and normotensive were 3.61 μg/kg (2.19–4.37 μg/kg) and 4.28 μg/kg (3.06–5.71 μg/kg), respectively. We observed a statistically significant increase in blood and placental cadmium levels in women with preeclampsia compared to healthy pregnant women. After adjusting for pre-pregnancy body mass index, maternal age, parity, gestational age at sample collection, and maternal calcium and magnesium levels, the odds ratio of having preeclampsia in the high tertile was markedly increased (odds ratio, 7.83 [95% CI, 1.64–37.26]) compared with the low tertile. Interestingly, there was no difference in the cadmium level in umbilical cord blood between the groups. Within the preeclamptic group, higher cadmium status was significantly associated with decreased birth weight. Our study suggested that elevated cadmium level in the maternal circulation could potentially increase the risk of preeclampsia. The results also demonstrate that higher cadmium status may contribute to fetal growth restriction in preeclamptic patients.     

Predictive value of cystatin C and beta-2 microglobulin in preeclampsia

The purpose of this study was to determine whether the levels of cystatin C and beta-2 microglobulin (B2M) are altered during the second trimester in the plasma of women who subsequently develop preeclampsia.Study designWe performed a case control study to compare the levels of cystatin C and B2M in women in whom preeclampsia ultimately developed (n = 30) and in pregnant women who remained normotensive throughout gestation (n = 60). The maternal plasma levels of cystatin C and B2M were measured by enzyme-linked immunosorbent assay. Blood samples were collected between 15 and 20 weeks’ gestation for fetal aneuploidy screening and frozen at ?20 °C until assay after groups had been selected.ResultsThe median concentrations of cystatin C and B2M were significantly higher in those who subsequently developed preeclampsia when compared to those of normal pregnancy (median 668.6 ng/ml and 418.3 μg/ml vs 413.7 ng/ml and 321.2 μg/ml, respectively).ConclusionsIn this study, the maternal plasma levels of cystatin C and B2M were significantly elevated in pregnant women who subsequently developed preeclampsia as compared with normotensive women. Alterations of these proteins antedate clinical symptoms and, thus, they may be useful for early identification of patients at the risk of developing preeclampsia.     

Maternal Height and Preterm Birth: A Study on 192,432 Swedish Women

BackgroundThere is increasing evidence that lower maternal stature is associated with shorter gestational length in the offspring. We examined the association between maternal height and the likelihood of delivering preterm babies in a large and homogeneous cohort of Swedish women.MethodsThis study covers antenatal data from the Swedish Medical Birth Register on 192,432 women (aged 26.0 years on average) born at term, from singleton pregnancies, and of Nordic ethnicity. Continuous associations between women''s heights and the likelihood of preterm birth in the offspring were evaluated. Stratified analyses were also carried out, separating women into different height categories.ResultsEvery cm decrease in maternal stature was associated with 0.2 days shortening of gestational age in the offspring (p<0.0001) and increasing odds of having a child born preterm (OR 1.03), very preterm (OR 1.03), or extremely preterm (OR 1.04). Besides, odds of all categories of preterm birth were highest among the shortest women but lowest among the tallest mothers. Specifically, women of short stature (≤155 cm or ≤-2.0 SDS below the population mean) had greater odds of having preterm (OR 1.65) or very preterm (OR 1.47) infants than women of average stature (-0.5 to 0.5 SDS). When compared to women of tall stature (≥179 cm), mothers of short stature had even greater odds of giving birth to preterm (OR 2.07) or very preterm (OR 2.16) infants.ConclusionsAmong Swedish women, decreasing height was associated with a progressive increase in the odds of having an infant born preterm. Maternal short stature is a likely contributing factor to idiopathic preterm births worldwide, possibly due to maternal anatomical constraints.     

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.     

Silibinin attenuates oxidative metabolism and cytokine production by monocytes from preeclamptic women

Abstract

Silibinin is a polyphenolic plant flavonoid with anti-inflammatory properties. The present study investigated the effect of silibinin on oxidative metabolism and cytokine production - tumor necrosis factor-alpha (TNF-α), interleukin (IL)12, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, IL-10, and transforming growth factor beta (TGF-β₁) - by peripheral blood monocytes (PBM) from preeclamptic pregnant women. It is a case-controlled study involving women with preeclampsia (PE, n = 30) compared with normotensive pregnant (NT, n = 30) and with non-pregnant (NP, n = 30) women. Monocytes were obtained and cultured with or without silibinin (5 μM or 50 μM) for 18 h. Superoxide anion (O₂?) and hydrogen peroxide (H₂O₂) release were determined by specific assays, and cytokine levels were determined by immunoenzymatic assays (ELISA). Monocytes from preeclamptic women cultured without stimulus released higher levels of O₂₂, H₂O₂ and TNF-α, and lower levels of IL-10 and TGF-β₁ than did monocytes from NT and NP women. Treatment in vitro with silibinin significantly inhibited spontaneous O₂? and H₂O₂ release and TNF-α production by monocytes from preeclamptic women. The main effect of silibinin was obtained at 50 μM concentration. Thus, silibinin exerts anti-oxidative and anti-inflammatory effects on monocytes from preeclamptic pregnant women by inhibiting the in vitro endogenous release of reactive oxygen species and TNF-α production.     

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.     

Increased serum heat-shock protein 70 levels reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia

It has been previously reported that serum levels of 70-kDa heat-shock protein (Hsp70) are elevated in preeclampsia. The aim of the present study was to examine whether increased serum Hsp70 levels are related to clinical characteristics and standard laboratory parameters of preeclamptic patients, as well as to markers of inflammation (C-reactive protein), endothelial activation (von Willebrand factor antigen) or endothelial injury (fibronectin), trophoblast debris (cell-free fetal DNA) and oxidative stress (malondialdehyde). Sixty-seven preeclamptic patients and 70 normotensive, healthy pregnant women were involved in this case-control study. Serum Hsp70 levels were measured with enzyme-linked immunosorbent assay (ELISA). Standard laboratory parameters (clinical chemistry) and C-reactive protein (CRP) levels were determined by an autoanalyzer using the manufacturer’s kits. Plasma von Willebrand factor antigen (VWF:Ag) levels were quantified by ELISA, and plasma fibronectin concentration by nephelometry. The amount of cell-free fetal DNA in maternal plasma was determined by quantitative real-time polymerase chain reaction analysis of the sex-determining region Y gene. Plasma malondialdehyde levels were measured by the thiobarbituric acid-based colorimetric assay. Serum Hsp70 levels were increased in preeclampsia. Furthermore, serum levels of blood urea nitrogen, creatinine, bilirubin and CRP, serum alanine aminotransferase and lactate dehydrogenase (LDH) activities, as well as plasma levels of VWF:Ag, fibronectin, cell-free fetal DNA and malondialdehyde were also significantly higher in preeclamptic patients than in normotensive, healthy pregnant women. In preeclamptic patients, serum Hsp70 levels showed significant correlations with serum CRP levels (Spearman R = 0.32, p = 0.010), serum aspartate aminotransferase (R = 0.32, p = 0.008) and LDH activities (R = 0.50, p < 0.001), as well as with plasma malondialdehyde levels (R = 0.25, p = 0.043). However, there was no other relationship between serum Hsp70 levels and clinical characteristics (age, parity, body mass index, blood pressure, gestational age, fetal birth weight) and laboratory parameters of preeclamptic patients, including markers of endothelial activation or injury and trophoblast debris. In conclusion, increased serum Hsp70 levels seem to reflect systemic inflammation, oxidative stress and hepatocellular injury in preeclampsia. Nevertheless, further studies are required to determine whether circulating Hsp70 plays a causative role in the pathogenesis of the disease.