Pre-eclampsia Concentrations Research Articles

Hepcidin concentrations and iron homeostasis in preeclampsia

Plasma iron is increased in preeclampsia (PE) when compared to healthy pregnant women. This is in contrast to inflammation characteristic for PE. The link between iron homeostasis and inflammation is hepcidin. Our goal was to describe hepcidin concentrations and its association with iron homeostasis in PE. We obtained peripheral blood samples from 30 preeclamptic [gestational age: 36.5 (24-40) weeks] and 37 healthy pregnant women [gestational age: 36 (28-39) weeks] to determine plasma hepcidin and interleukin-6 (IL-6) concentrations, complete blood cell counts and parameters of iron homeostasis [plasma iron, transferrin and ferritin levels and total iron binding capacity (TIBC)]. Hepcidin was measured using mass spectrophotometry. The Mann-Whitney test was used for statistical analysis. Plasma hepcidin, IL-6, iron and ferritin concentrations were increased (p<0.05 for all), whereas plasma transferrin, TIBC and mean corpuscular hemoglobin concentrations were lower (p<0.05 for all) in PE compared to healthy pregnant women. No differences were seen in the other parameters investigated. Plasma iron concentrations are increased despite high hepcidin concentrations in PE. This might indicate a resistance to the iron-decreasing action of hepcidin.

Interethnic differences in ADMA concentrations and negative association with nitric oxide formation in preeclampsia

Recent studies have suggested that impaired nitric oxide (NO) formation in preeclampsia may result from increased concentrations of an endogenous NO synthase inhibitor, the asymmetric dimethylarginine (ADMA). However, no previous study has examined whether a negative association exists between ADMA and nitrite concentrations in preeclampsia. Moreover, no previous study has compared ADMA and nitrite levels in black and white preeclamptic pregnant women. We measured plasma nitrite concentrations using an ozone-based chemiluminescence assay, and plasma ADMA levels using enzyme immunoassays in 94 pregnant (47 healthy pregnant: 16 blacks and 31 whites; and 47 preeclamptic: 14 blacks and 33 whites). We found higher ADMA (2.199 + or -0.016 micromol/l vs. 2.112 + or - 0.012 micromol/l; P<0.0001) and lower plasma nitrite levels (102 + or - 7.1 nmol/l vs. 214.8 + or - 26.1 nmol/l; P<0.0001) in preeclamptic compared with healthy pregnant women. Black pregnant had higher ADMA levels than white pregnant women (P<0.05), both in preeclamptic (2.239 + or - 0.020 micromol/l vs. 2.144 + or - 0.019 micromol/l) and in healthy pregnant (2.172 + or - 0.025 micromol/l vs. 2.077 + or - 0.018 micromol/l). Conversely, we found no significant effects of ethnicity on the plasma nitrite levels, both in healthy pregnant and in preeclamptic women (P>0.05). We found a significant negative correlation (P<0.05) between these markers (r=-0.28; P<0.05). Our findings show higher ADMA and lower nitrite levels in preeclamptic compared with healthy pregnant, and the concentrations of these biomarkers are inversely associated. While ethnicity affected ADMA concentrations, no such effect was found with respect to nitrite levels. These results may have important implications for studies on NO biology and therapeutic approaches of preeclampsia.

Increased Maternal Serum and Cord Blood Fibronectin Concentrations in Preeclampsia are Associated with Higher Placental Hyaluronic Acid and Hydroxyproline Content

Background. Total or cellular fibronectin (FN) determinations have been used to differentiate between normal and preeclamptic pregnants. The purpose of this study was to examine the relationship between maternal serum FN levels and the extracellular matrix molecule contents of placental tissue, such as FN, hyaluronic acid (HA) and hydroxyproline (HP) levels. Material and Methods. We obtained maternal blood samples and placental tissue samples from healthy (n = 17, controls) and preeclamptic pregnants (n = 29). We also obtained cord blood samples for FN and HA determination from the same patients. FN and HA concentrations in the placenta and maternal and cord blood were measured by and enzyme-linked immunosorbent assay and HP contents in the placenta were measured by a colorimetric assay. Results. FN levels in maternal serum, cord blood, and placenta were significantly higher in preeclamptics than in controls (p<0.001, p<0.001 and p<0.05, respectively). HA concentrations in the cord blood and placenta were found to be elevated in preeclamptics (p<0.05 and p<0.01). Preeclamptics had significantly higher placental HP levels than controls (p<0.001). Similar statistically significant results were obtained when the pregnant subjects classified as nulliparous and multiparous. There was no difference in ECM molecule levels between nulliporous and multiparous women in preeclamptic pregnant group. In regression analysis maternal serum FN levels were correlated with placental HA and HP levels (p<0.01 and p<0.01). There was a positive correlation between cord blood FN and both placental HP (p<001) and HA levels (p<0.01). FN levels in maternal serum, cord blood, and placenta were also negative correlated with fetal birth weight (p<0.01, p<0.05 and p<0.05, respectively). Conclusion. FN in maternal serum, cord blood, and placenta is increased with elevated placental HA and HP levels, probably reflecting placental basement membrane alterations during preeclampsia.

Plasma osteopontin concentrations in preeclampsia – is there an association with endothelial injury?

Abstract Background: It has been previously reported that plasma osteopontin (OPN) concentrations are increased in cardiovascular disorders. The goal of the present study was to determine plasma OPN concentrations in healthy pregnant women and preeclamptic patients, and to investigate their relationship to the clinical characteristics of the study subjects and to markers of inflammation [C-reactive protein (CRP)], endothelial activation [von Willebrand factor antigen (VWF:Ag)] or endothelial injury (fibronectin), oxidative stress [malondialdehyde (MDA)] and trophoblast debris (cell-free fetal DNA). Forty-four patients with preeclampsia and 44 healthy pregnant women matched for age and gestational age were involved in this case-control study. Plasma OPN concentrations were measured with ELISA. Serum CRP concentrations were determined with an autoanalyzer using the manufacturer's reagents. Plasma VWF:Ag was quantified by ELISA, while plasma fibronectin concentrations were measured by nephelometry. Plasma MDA concentrations were estimated by the thiobarbituric acid-based colorimetric assay. The amount of cell-free fetal DNA in maternal plasma was determined by quantitative real-time PCR analysis of the sex-determining region Y (SRY) gene. For statistical analyses, non-parametric methods were applied. Serum levels of CRP, as well as plasma concentrations of VWF:Ag, fibronectin, MDA and cell-free fetal DNA were significantly higher in preeclamptic patients than in healthy pregnant women. There was no significant difference in plasma OPN concentrations between controls and the preeclamptic group. However, preeclamptic patients with plasma fibronectin concentrations in the upper quartile had significantly higher plasma OPN concentrations than those below the 75th percentile, as well as healthy pregnant women [median (interquartile range): 9.38 (8.10-11.99) vs. 7.54 (6.31-9.40) and 7.40 (6.51-8.80) ng/mL, respectively, p<0.05 for both]. Furthermore, in preeclamptic patients, plasma OPN concentrations showed a significant positive linear association with plasma fibronectin (Spearman R=0.38, standardized regression coefficient (beta)=0.41, p<0.05 for both). Plasma OPN concentrations are increased in preeclamptic patients with extensive endothelial injury. However, further studies are warranted to explore the relationship between OPN and endothelial damage. Clin Chem Lab Med 2010;48:181-7.

Circulating and Uteroplacental Adipocytokine Concentrations in Preeclampsia

The adipokines adiponectin and leptin may contribute to preeclampsia; however, the reports are conflicting. We explored the issue further. We studied 25 pregnant women with normal pregnancy in first, 25 in second, and 30 in third trimesters, 15 healthy nonpregnant women, and 32 women with preeclampsia. We used enzyme-linked immunosorbent assay to measure human plasma adiponectin (ng/mL) and leptin (ng/mL) concentrations. We also investigated adiponectin and leptin expression by quantitative messenger RNA in fat, decidua, and placenta tissues in a second study. Prepregnancy body mass index was not different in preeclamptic and nonpreeclamptic women. Plasma adiponectin concentrations increased throughout normal pregnancy, compared to nonpregnant women. The values increased in every trimester but were invariably lower in women with preeclampsia. Adiponectin nonetheless correlated inversely with prepregnancy body mass index. Such correlations were not found in women with preeclampsia. Plasma leptin in contrast decreased during pregnancy in every trimester. Leptin values were much higher in preeclamptic than in nonpreeclamptic women. Leptin expression was increased in the uteroplacental unit and in fat tissue of preeclamptic, compared to nonpreeclamptic women, while no differences in adiponectin expression were found. Adiponectin increases in normal pregnancy but remains correlated with prepregnancy body mass index. Plasma leptin decreases in normal pregnancy. In preeclamptic women, the normal adipokine responses are perturbed and this could be of pathophysiological significance.

Association of Paraoxonase 55 and 192 Gene Polymorphisms on Serum Homocysteine Concentrations in Preeclampsia

Paraoxonase 1 (PON1) is thought to influence serum homocysteine concentrations, at least in part, due to its homocysteine thiolactonase activity and to play a role in preeclampsia and atherosclerosis. We investigated the effects of PON 55 and PON 192 polymorphisms on plasma total homocysteine (tHcy) concentrations in preeclamptic and healthy pregnants among Turkish population (N = 106). PON 55 and 192 genotypes were determined by PCR RFLP techniques. Plasma tHcy concentrations were measured by high-performance liquid chromatography. No differences were observed in the distribution of PON 1 55/192 genotypes and allele frequencies between the preeclamptic and healthy pregnants. tHcy level in the plasma of preeclamptic women was found to be increased in comparison with healthy pregnants (P &lt; 0.01). Preeclamptic women bearing the mutated PON 192 RR and wild-type PON1 55 LL genotypes had higher tHcy levels than those of the healthy pregnants with the corresponding genotypes, supporting the possibility that the hyperhomocysteinaemia seen in preeclamptic women is associated with the PON genotypes. However, no influence of the allelic distribution on plasma tHcy concentrations was detected in either group. Our results suggest that PON1 55 and 192 genotypes might have an important role in developing hyperhomocysteinaemia and may also have a role in the pathogenesis of preeclampsia in a Turkish population.

Serum Levels of Angiopoietin-Related Growth Factor Are Increased in Preeclampsia

Preeclampsia is a serious complication in pregnancy with an increased future cardiovascular and metabolic risk for both mother and newborn. Recently, angiopoietin-related growth factor (AGF) was introduced as a novel liver-derived protein with proangiogenic and insulin-sensitizing effects. In the current study, we hypothesized that serum levels of AGF would be lower in preeclamptic patients as compared to healthy controls. AGF was quantified by enzyme-linked immunosorbent assay (ELISA) in control and preeclamptic patients during pregnancy ( n =22, Preeclampsia: n =22) and 6 months after delivery ( n =20, Preeclampsia: n =20). Furthermore, circulating AGF was correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. During pregnancy, median maternal AGF concentrations were significantly higher in preeclampsia (191.6 microg/l) as compared to control subjects (136.3 microg/l) (P = 0.004). Furthermore, preeclampsia and systolic blood pressure (SBP) were associated with AGF levels in multivariate analyses independent of maternal age. However, higher circulating AGF concentrations in preeclampsia did not persist 6 months after delivery. Maternal AGF serum levels are significantly and paradoxically higher in preeclampsia during pregnancy. However, median postpartum circulating AGF levels are similar in preeclampsia and normal pregnancies.

Blood pressure augmentation and maternal circulating concentrations of angiogenic factors at delivery in preeclamptic and uncomplicated pregnancies

The objective of the study was to determine whether blood pressure increases are associated with maternal angiogenic factors in uncomplicated and preeclamptic pregnancies. Associations of blood pressure increases from mid- to late pregnancy with maternal serum concentrations of soluble fms-like tyrosine kinase receptor (sFlt1), soluble endoglin (sEng), and placental growth factor (PlGF) at delivery were analyzed in 43 uncomplicated and 44 preeclamptic pregnancies. In uncomplicated pregnancies, increases in diastolic and mean arterial pressure were inversely associated with PlGF at delivery and positively associated with sEng and sFlt1/PlGF ratio. There were no significant associations between blood pressure increases and angiogenic factor concentrations in preeclampsia. These data suggest that angiogenic factors are involved in blood pressure modulation in normotensive pregnancy and are consistent with the hypothesis that angiogenic balance plays a role in maternal breast cancer risk reduction associated with mid- to late blood pressure increases in uncomplicated pregnancies.

Nitric Oxide Formation Is Inversely Related to Serum Levels of Antiangiogenic Factors Soluble Fms-Like Tyrosine Kinase-1 and Soluble Endogline in Preeclampsia

Deficient NO formation has been implicated in hypertensive disorders of pregnancy. However, no previous study has compared the circulating nitrite concentrations in healthy pregnant women with those found in hypertensive disorders of pregnancy. Moreover, 2 antiangiogenic factors produced in the placenta (soluble fms-like tyrosine kinase-1 and soluble endogline) may affect NO formation during pregnancy. Here, we hypothesized that lower concentrations of markers of NO formation exist in hypertensive disorders of pregnancy and that inverse relationships exist between these markers and soluble fms-like tyrosine kinase-1 or soluble endogline. In this cross-sectional study, we compared 58 healthy pregnant women with 56 gestational hypertensive subjects and 45 preeclamptic patients. We measured plasma and whole blood nitrite concentrations using an ozone-based chemiluminescence assay and serum soluble fms-like tyrosine kinase-1 and soluble endogline concentrations using enzyme immunoassays. Whole blood nitrite levels were significantly lower in gestational hypertensive subjects and preeclamptic patients (-36% and -58%, respectively; both P<0.05) compared with healthy pregnant women. The plasma nitrite levels were approximately 37% lower in both groups with hypertensive disorders of pregnancy compared with the group with normotensive pregnancies (both P<0.05). As expected, we found higher circulating soluble fms-like tyrosine kinase-1 and soluble endogline concentrations in preeclampsia compared with gestational hypertensive subjects or with healthy pregnancies (both P<0.05). We found negative correlations between antiangiogenic factors and plasma or whole blood nitrite concentrations (Spearman's r from -0.175 to -0.226; all P<0.05). Our results show clinical evidence for impaired NO formation in preeclampsia or gestational hypertension. The negative correlations between markers of NO formation and antiangiogenic factors in preeclamptic patients suggest an inhibitory effect for these factors on NO formation.

Circulating concentrations of soluble endoglin (CD105) in fetal and maternal serum and in amniotic fluid in preeclampsia

We explored whether concentrations of soluble endoglin in fetal serum and amniotic fluid and in maternal serum were elevated in preeclampsia. Umbilical vein serum, amniotic fluid, and maternal serum from 42 preeclamptic and 43 uncomplicated pregnancies that were delivered by cesarean section were analyzed by enzyme-linked immunosorbent assay for soluble endoglin. Median maternal serum and amniotic fluid soluble endoglin concentrations were elevated in preeclampsia, compared with control pregnancies (66.9 ng/mL vs 15.1 ng/mL; P < .001, and 1.9 ng/mL vs 0.6 ng/mL; P < .001). Low concentrations of soluble endoglin were found in fetal circulation, which did not differ between preeclampsia and control pregnancies (5.0 ng/mL vs 4.7 ng/mL; P = .2). Maternal serum soluble endoglin levels correlated with circulating soluble fms-like tyrosine kinase 1 concentrations. We confirmed elevated soluble endoglin in maternal circulation in preeclampsia, which correlated with soluble fms-like tyrosine kinase 1 concentrations and soluble fms-like tyrosine kinase 1/placental growth factor ratio. The fetus appears not to contribute to elevated circulating maternal soluble endoglin concentrations in preeclampsia.

Natriuretic peptides and hemodynamics in preeclampsia

The purpose of this study was to evaluate the relationship between natriuretic peptides (NT-proANP and NT-proBNP) and hemodynamic parameters in preeclampsia. This was a cross-sectional study of 19 preeclamptic, 15 chronic hypertensive, and 26 normotensive women in the third trimester of pregnancy. Stroke index (SI), heart rate (HR), cardiac index (CI), systemic vascular resistance index (SVRI), and left cardiac work index (LCWI) were derived by whole-body impedance cardiography. Systolic blood pressure (SAP), diastolic blood pressure (DAP), and mean arterial pressure (MAP) were measured. The plasma levels of NT-proANP and NT-proBNP were determined with radioimmunoassays. NT-proANP and NT-proBNP concentrations were significantly higher in preeclamptic women compared to chronic hypertensive and normotensive pregnancies. Preeclamptic women had lower CI and HR and higher SAP, MAP, and SVRI than the control groups. In preeclampsia NT-proANP correlated significantly with SAP and SVRI; meanwhile, NT-proBNP correlated significantly with SVRI and CI. These correlations persisted in the subgroup of nonmedicated preeclamptic women, except in the case of NT-proBNP and CI. High NT-proANP and NT-proBNP concentrations in preeclampsia reflect the strain on the heart caused by high afterload, rather than the function of the heart expressed as SI or CI.

Maternal Leptin Concentrations are Similar in African Americans and Caucasians in Normal Pregnancy, Preeclampsia and Small-for-Gestational-Age Infants

Leptin concentrations were measured in African American women in order to assess leptin's role in the increased frequency and severity of preeclampsia. In addition, leptin concentrations were measured in women who delivered small-for-gestational-age (SGA) infants. A case-control study of African American and Caucasian women with normal pregnancies, preeclampsia, or SGA infants was done. Plasma leptin was quantitated by radio-immunoassay. The previously recognized pattern of increased leptin concentrations in preeclampsia was replicated. Leptin concentrations did not differ by race in any diagnostic category, and concentrations in women with SGA infants were not higher than those in healthy women. Differences in the frequency and severity of preeclampsia in African Americans cannot be explained by higher leptin concentrations.

Preeclampsia and SGA are characterized by low concentrations of a novel factor involved in angiogenesis and endothelial cell function: sVEGFR-2

A NOVEL FACTOR INVOLVED IN ANGIOGENESIS AND ENDOTHELIAL CELL FUNCTION: SVEGFR-2 TINNAKORN CHAIWORAPONGSA, JIMMY ESPINOZA, JYH KAE NIEN, LUIS GONCALVES, SAMUEL EDWIN, KARINA RICHANI, ELEAZAR SOTO, JOAQUIN SANTOLAYA, CHONG JAI KIM, YEON MEE KIM, ROBERTO ROMERO, Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, Michigan, Perinatology Research Branch, NICHD, NIH, DHHS, Bethesda, Maryland, Wayne State University School of Medicine, Department of Pathology, Detroit, Michigan OBJECTIVE: Preeclampsia (PE) is considered to be an anti-angiogenic state. A role for soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) has been proposed (JCI 2003 and NEJM 2004). Recently, sVEGFR-2 has been detected in plasma (Mol Can Res 2004;2:315). The recombinant form of this protein has anti-angiogenic activity. There is no information on plasma sVEGFR-2 concentration in PE. This study was conducted to determine if PE and small-for-gestational age (SGA) neonates without PE are associated with changes in the maternal plasma concentration of sVEGFR-2. STUDY DESIGN: This cross-sectional study included normal pregnant women (n=135), patients with SGA (n=53), and women with PE (n=112). SGA was defined as an ultrasound-estimated fetal weight below the 10th percentile for gestational age, confirmed by neonatal birthweight. Plasma concentrations of sVEGFR-2 were determined by ELISA. Parametric statistics were used for analysis. RESULTS: 1) Patients with PE and those with SGA without PE had a lower mean plasma concentration of sVEGFR-2 than normal pregnant women (PE mean G SD: 8.3G3.3 ng/ml vs. normal pregnancy mean G SD: 11.4G4.2 ng/ ml and SGA mean G SD: 7.7G1.7 ng/ml vs. normal pregnancy mean G SD: 11.4G4.2 ng/ml; p!0.001 for both); and 2) There was no significant difference in the mean plasma concentration of sVEGFR-2 in patients with PE and those with SGA (p=0.9). CONCLUSION: 1) PE and SGA are associated with decreased plasma concentrations of sVEGFR-2; and 2) One interpretation of the findings is that plasma sVEGFR-2 concentration could be a marker of endothelial cell function in maternal circulation because the transmembrane isoform of this protein is essential for endothelial cell survival.

Circulating concentrations of sFlt1 (soluble fms-like tyrosine kinase 1) in fetal and maternal serum during pre-eclampsia

Objective:We hypothesized that umbilical vein serum soluble fms-like tyrosine kinase 1 (sFlt1) concentration was augmented in pre-eclampsia. We also explored a possible association between fetal and maternal concentrations of sFlt1. Study design:At cesarean delivery, maternal serum samples from pre-eclamptic (n=38) and uncomplicated (n=32) pregnancies were obtained, as well as umbilical vein serum and amniotic fluid samples. ELISA for human sFlt1, vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were performed. Results:Median sFlt1 concentrations were elevated in pre-eclampsia compared to uncomplicated pregnancy, in umbilical venous serum (246 and 163pg/mL, P=0.04), in maternal serum (9932 and 3417pg/mL, P<0.001), as well as in amniotic fluid (51,040 and 33,490pg/mL, P=0.03). A positive association between the fetal and maternal serum levels of sFlt1 was found in the pre-eclampsia group. Median PlGF concentration in the maternal serum was significantly lower in the pre-eclampsia group compared to the control group (82pg/mL and 169pg/mL, P<0.001). Conclusions:sFlt1 concentration is elevated in the fetal circulation in pre-eclampsia, but at a much lower level than in the maternal circulation. The results of our study do not support a substantial fetal contribution to the elevated circulating maternal sFlt1 protein concentration in pre-eclampsia.

Oxidative stress and preeclampsia: rationale for antioxidant clinical trials.

Preeclampsia remains a frequent and potentially dangerous complication of pregnancy. The cause remains largely unknown, but oxidative stress and a generalized inflammatory state are features of the maternal syndrome. The placenta appears to be the principal source of free radical synthesis but maternal leukocytes and the maternal endothelium are also likely contributors. Recent reports have suggested an important role for placental trophoblast NAD(P)H oxidase in free radical generation in preeclampsia. The antioxidant vitamin E is now known to have multiple actions in addition to prevention of lipid peroxidation (ie, inhibition of NAD(P)H oxidase activation and the inflammatory response). In view of the abnormally low plasma vitamin C concentrations in preeclampsia, a combination of vitamins C and E is a promising prophylactic strategy for prevention of preeclampsia. Several multicenter randomized clinical trials are now underway. The potential use of antioxidants and the recognized, albeit modest, benefit of low-dose aspirin prophylaxis have heightened the need for a reliable predictive test for preeclampsia. A combination test involving several relevant biomarkers is likely to provide the best predictive potential.

Response: Adiponectin Concentrations in Preeclampsia

HomeHypertensionVol. 0, No. 1Response: Adiponectin Concentrations in Preeclampsia Free AccessOtherPDF/EPUBAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessOtherPDF/EPUBResponse: Adiponectin Concentrations in Preeclampsia Naveed Sattar, Jane Ramsey, Nigel Jamieson and Ian A. Greer Naveed SattarNaveed Sattar Search for more papers by this author , Jane RamseyJane Ramsey Search for more papers by this author , Nigel JamiesonNigel Jamieson Search for more papers by this author and Ian A. GreerIan A. Greer Search for more papers by this author Originally published2 Feb 2004https://doi.org/10.1161/01.HYP.0000118059.61838.b9Hypertension. 2004;0Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: August 1, 2018: Ahead of Print "Response: Adiponectin Concentrations in Preeclampsia." Hypertension, , pp. – Previous Back to top Next FiguresReferencesRelatedDetails January 2019Vol 0, Issue 1 Advertisement Article InformationMetrics https://doi.org/10.1161/01.HYP.0000118059.61838.b9 Originally publishedFebruary 2, 2004 PDF download Advertisement

High levels of urinary vascular endothelial growth factor in women with severe preeclampsia

Elevated plasma VEGF concentrations in preeclampsia are associated with local placental ischemia and endothelial dysfunction. We investigated the urinary VEGF excretion in women with severe preeclampsia (n=37) and its relation with proteinuria compared to that in healthy pregnant (n=32) and non-pregnant women (n=30). In women with severe preeclampsia VEGF levels were 54.0 (19.9-192.4) ng/mmol creatinine, significantly (p<0.0001) higher than levels in pregnant controls (28.2 (6.7-63.0) ng/mmol creatinine) and non-pregnant controls (29.5 (10.1-59.1) ng/mmol creatinine). Proteinuria was not significantly correlated with urinary VEGF levels. In conclusion, high urinary VEGF concentrations in severe preeclampsia might reflect increased renal production of VEGF rather than elevated VEGF levels in the systemic circulation.

High levels of urinary vascular endothelial growth factor in women with severe preeclampsia.

Elevated plasma VEGF concentrations in preeclampsia are associated with local placental ischemia and endothelial dysfunction. We investigated the urinary VEGF excretion in women with severe preeclampsia (n=37) and its relation with proteinuria compared to that in healthy pregnant (n=32) and non-pregnant women (n=30). In women with severe preeclampsia VEGF levels were 54.0 (19.9-192.4) ng/mmol creatinine, significantly (p<0.0001) higher than levels in pregnant controls (28.2 (6.7-63.0) ng/mmol creatinine) and non-pregnant controls (29.5 (10.1-59.1) ng/mmol creatinine). Proteinuria was not significantly correlated with urinary VEGF levels. In conclusion, high urinary VEGF concentrations in severe preeclampsia might reflect increased renal production of VEGF rather than elevated VEGF levels in the systemic circulation.

Neutrophil Activation and C‐Reactive Protein Concentration in Preeclampsia

Preeclamptic pregnancies seem to be associated with a higher extent of inflammation compared with normal ones. We intended to test this proposal and also to clarify the contribution of some variables in such inflammatory process.We measured total and differential leukocyte count, serum C‐reactive protein (CRP), and plasma levels of lactoferrin, elastase, and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Uric acid was also evaluated and used as an indicator of the severity of the disease. A cross‐sectional study was performed by evaluating healthy and preeclamptic women in the third trimester of gestation (n = 67 and n = 51, respectively) and 24 to 48 h postpartum (n = 32 and n = 26, respectively).When comparing the third trimester of normal and preeclamptic pregnancies, we found significantly higher levels of uric acid, CRP, and elastase, and a significantly higher elastase to neutrophil ratio in the pathologic group. However, for CRP, statistical significance was lost after adjustment for maternal weight. No significant differences were found in total leukocyte count, plasma levels of GM‐CSF, and lactoferrin between groups. In preeclampsia, a significant positive correlation was found between elastase and lactoferrin and these neutrophil activation products correlated positively with uric acid level. Considering the analysis of all variables in the postpartum period, only CRP and uric acid levels were significantly elevated in the pathologic group. However, CRP differences obtained in the puerperium seem to be influenced by the increased number of dystocic deliveries in the preeclamptic group.In conclusion, our data suggest that inflammation is further pronounced in preeclampsia and that the extent of neutrophil activation correlates with the severity of this syndrome.

Relation between adenosine and T-helper 1/T-helper 2 imbalance in women with preeclampsia

OBJECTIVE: To evaluate the relationship between changes in plasma adenosine concentration and imbalances in the T-helper 1/T-helper 2 ratio in peripheral blood of women with preeclampsia. METHODS: Plasma adenosine concentrations and the T-helper 1/T-helper 2 ratio were examined in the peripheral blood of 16 preeclamptic and normal pregnant women. The proportion of specific T-cell marker CD4-positive cells expressing intracellular cytokines, interferon-γ derived from T-helper 1 and interleukin-4 derived from T-helper 2 cells, were analyzed by flow cytometry. The ratio of interferon-γ secreting cells to interleukin-4 secreting cells was taken as the T-helper 1/T-helper 2 ratio in vivo. The effect of the adenosine-receptor blocker 8-sulfophenyltheophylline was also measured in vitro. RESULTS: Mean plasma adenosine concentration in preeclampsia was significantly higher than that in normal pregnancy (0.68 ± 0.07 μmol/L versus 0.39 ± 0.06 μmol/L, P < .05). The proportions of interferon-γ secreting cells increased and interleukin-4 secreting cells decreased significantly in preeclampsia, and the T-helper 1/T-helper 2 ratio in preeclampsia was significantly higher than in normal pregnancy (18.1 ± 2.6 versus 9.9 ± 1.5, P < .05). The increase of the proportion of interferon-γ secreting cells after adenosine receptor blockade in preeclampsia significantly exceeded that of normal pregnancy. The T-helper 1/T-helper 2 ratio in preeclampsia was significantly greater than that in normal pregnancy (36% versus 17%, P < .05). CONCLUSION: Increased plasma adenosine may be involved in the regulation of imbalances in the T-helper 1/T-helper 2 ratio in women with preeclampsia.