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.     

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.     

Reduced placental docosahexaenoic acid levels associated with increased levels of sFlt-1 in preeclampsia

Our earlier studies, in preeclamptic women have shown altered levels of long chain polyunsaturated fatty acids (LCPUFA), essential constituents of the cell membrane lipids responsible for membrane stability as one of the key factors contributing to the pathophysiology of preeclampsia. We have also reported elevated levels of sFlt-1 in preeclampsia. The present study examines the levels of LCPUFA and their association with sFlt-1 levels in 69 pre-eclamptic women and 40 normotensive women. DHA and omega 3 fatty acid levels were lower (p<0.001) while arachidonic acid and omega 6 fatty acid levels were higher (p<0.05) in preeclamptic women as compared to normotensive women. Maternal plasma sFlt-1 levels were higher (p<0.05) in preeclamptic women and were negatively associated with DHA (p=0.008) and omega 3 fatty acids concentrations (p=0.031). Our results suggest that altered placental LCPUFA may result in altered membrane lipid fatty acid composition leading to increased release of sFlt-1 in circulation.     

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.     

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.     

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.     

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.     

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.     

Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness

Several examples of functional G-protein-coupled receptor heterodimers have been identified. However, it is not known whether receptor heterodimerization is involved in the pathogenesis of human disorders. Here we show that in preeclamptic hypertensive women, a significant increase in heterodimerization occurs between the AT(1)-receptor for the vasopressor angiotensin II and the B(2)-receptor for the vasodepressor bradykinin. AT(1)-B(2)-receptor heterodimerization in preeclampsia correlated with a 4-5-fold increase in B(2)-receptor protein levels. Expression of the AT(1)-B(2) heterodimer increased the responsiveness to angiotensin II and conferred resistance in AT(1)-receptors to inactivation by reactive oxygen species raised in normotensive and preeclamptic pregnancies. We suggest that AT(1)-B(2) heterodimers contribute to angiotensin II hypersensitivity in preeclampsia. Moreover, we identify preeclampsia as the first disorder associated with altered G-protein-coupled receptor heterodimerization.     

The plasma membrane Ca2+-ATPase protein from red blood cells is not modified in preeclampsia

Plasma membrane Ca2+-ATPase activity diminishes by about 50% in red blood cells during preeclampsia. We investigated whether the number of Ca2+-ATPase molecules is modified in red cell membranes from preeclamptic pregnant women by measuring the specific phosphorylated intermediate of this enzyme. Also, we isolated the Ca2+-ATPase protein from both normotensive and preeclamptic pregnant women and estimated its molecular weight, and its cross-reactions with specific polyclonal and monoclonal (5F10) antibodies against it. We measured the Ca2+-ATPase activity in a purified state and the effect of known modulators of this ATPase. It was found that the phosphorylated intermediate associated with PMCA is similar for red cell ghosts from normotensive and preeclamptic women, suggesting a similar number of ATPase molecules in these membranes. The molecular weight of the Ca2+-ATPase is around 140 kDa for both normotensive and preeclamptic membranes, and its cross-reactions with specific antibodies is similar, suggesting that the protein structure remains intact in preeclampsia. Calmodulin, ethanol, or both calmodulin plus ethanol, stimulated the Ca2+-ATPase activity to the same extent for both normotensive and preeclamptic preparations. Our results showed that the reduced Ca2+-ATPase activity of the red cell membranes from preeclamptic women is not associated with a defective enzyme, but rather with a high level of lipid peroxidation.     

Increased levels of serum macrophage colony-stimulating factor before the onset of preeclampsia.

Macrophage colony-stimulating factor (M-CSF) is known to play a central role in maintaining pregnancy. The present study determined whether the increase in serum M-CSF levels preceded the onset of preeclampsia. Blood was collected from 110 normotensive pregnant women at risk for preeclampsia who were carrying single fetuses at about 30 weeks of gestation. After centrifugation, serum was stored at -20 degrees C until assay. Eighteen women developed preeclampsia at a later stage of pregnancy (group 1), while 88 women continued to have normotensive pregnancies until delivery. Thirty-four of the 88 women with normotensive pregnancy who were matched for age and parity were selected to form a control group (group 2). Serum M-CSF levels were determined by the sandwich ELISA method using three antibodies. Serum level of M-CSF was 1,266 U/ml (median) in group 1 and 1,082 U/ml in group 2. Serum M-CSF levels were significantly higher in group 1 than in group 2 (p < 0.0002). Increased levels of serum M-CSF markedly precede the development of clinical manifestations of preeclampsia. High serum M-CSF levels support M-CSF elevation in the placenta. This elevation at 30 weeks of gestation may be associated with placental hypoxia, which is considered the cause of preeclampsia.     

Neurokinin B causes concentration-dependent relaxation of isolated human placental resistance vessels

Placental neurokinin B (NKB) was recently identified as the causative agent in preeclampsia, a condition characterized by increased maternal and feto-placental vascular resistance. We hypothesized that NKB should constrict placental resistance vessels. Placentas were obtained from normotensive pregnancies. Immediately after delivery, stem villous arteries (300 microm diameter, 1.2 mm long) were dissected from macroscopically normal tissue in cold HEPES-physiological salt solution (PSS), mounted on a wire myograph system, and bathed in HEPES-PSS at 37 degrees C. After determination of the passive-tension internal circumference characteristics, the arteries were set to 90% of the internal circumference they would have under a normal physiological transmural pressure. Cumulative concentration-response curves were constructed for NKB (1 x 10(-12) to 1 x 10(-5) mol/l). Since there was no constrictive response to NKB, cumulative constrictive concentration-response curves were constructed to the thromboxane A(2) mimetic U46619 (1 x 10(-9) to 1 x 10(-5) mol/l). The vessels were then pre-constricted to 80% of maximal response and exposed to cumulative concentrations of NKB (1 x 10(-12) to 1 x 10(-6) mol/l). NKB caused a concentration-dependent relaxation (Maximal response NKB, 51+/-5%, n=5; time control, 12+/-6%, n=4; P<0.05). Removal of the endothelium did not alter the vasodilatory response to NKB. We conclude that, contrary to our hypothesis, NKB causes an endothelium-independent relaxation of the placental resistance vessels. We propose that NKB plays a role in the maintenance of high placental blood flow in normal pregnancy.     

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.     

Proteome analysis reveals elevated serum levels of clusterin in patients with preeclampsia

Preeclampsia is a pregnancy-specific syndrome and a major cause of maternal mortality. The pathophysiology of preeclampsia is unknown, and no proteome analysis of preeclampsia has been reported. We sought to identify proteins associated with preeclampsia using a proteomic technique and performed two-dimensional electrophoresis (2-DE) on sera from six patients with preeclampsia and six normal pregnant women, followed by comparison of the SYPRO Ruby-stained 2-DE profiles. A group of overexpressed spots was identified in the limited study set. Overexpressed spots were identified as clusterin by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) followed by peptide mass fingerprinting, a protein database search, and Western blot analysis. Additionally, sera of 80 preeclamptic women and 80 normal pregnant women were processed by immunoassay methods to confirm changes in clusterin concentrations quantitatively. Immunoassays showed that clusterin levels in the 80 preeclamptic women were significantly higher than those in the 80 controls (mean +/- SD; 1.62 +/- 0.46 times reference level in preeclamptic women vs. 1.30 +/- 0.46 times reference level in controls, P < 0.001). Proteomic analysis of serum proteins is a promising tool for studying preeclampsia pathophysiology and identifying proteins associated with preeclampsia.     

Gene analysis of the N-terminal region of the estrogen receptor alpha in preeclampsia

Alterations in the NH(2)-terminal region of the estrogen receptor alpha (ERalpha) gene expressed in placental bed tissue may be implicated in the development of preeclampsia, the pathogenesis of which involves the spiral arteries. Therefore, mutations and polymorphisms on exons 1 and 2 of the gene encoding ERalpha were studied. Placental bed biopsies were taken from 20 healthy, normotensive pregnant women and 16 preeclamptic patients. DNA was extracted from the tissue and exon 1 and exon 2 were amplified by PCR prior to denaturing gradient gel electrophoresis analysis or to single stranded conformational polymorphism analysis. In exon 1, a codon 10 polymorphism, either homozygous for the wild type gene, homozygous for the mutant type gene, or heterozygous, was revealed in both patients and healthy individuals. A codon 87 polymorphism, homozygous for the wild type gene, was detected in both groups. No mutations or polymorphisms were found in exon 2. The allele distribution for either codon 10 or 87 between patients and healthy individuals showed no significant differences. In conclusion, genetic alterations in the NH(2)-terminal region of the ERalpha molecule are not correlated with preeclampsia.     

Newborns of Preeclamptic Women Show Evidence of Sex-Specific Disparity in Fetal Growth

BackgroundEvidence suggests that in response to in utero insults, male versus female infants have greater disadvantages in pregnancy outcome. In addition, there is a growing body of evidence suggesting that there is a sex-specific fetal response to maternal disease during pregnancy. We considered that a sex-specific relationship may exist between preeclampsia and reduced fetal growth.ObjectiveWe investigated if the relationship between preeclampsia and fetal growth was modified by fetal sex.MethodsWe limited the study population to singleton pregnancies of black and white normotensive and preeeclamptic women enrolled in the Collaborative Perinatal Project (1959–1965). The patients were offspring of 516 preeclamptic and 8801 normotensive women. After adjustment for confounders, interaction terms between preeclamptic status and fetal sex were evaluated to determine if the influence of preeclampsia on fetal growth varied with fetal sex. Separate linear and logistic regression models were then fitted for males and females to report the estimate of the relationship between preeclampsia and fetal growth by fetal sex. The results were stratified by preterm status (<37 vs ≥37 completed weeks of gestation). The mean head and chest circumferences, birthweight, ponderal index, and frequency of small for gestational age were examined. A 2-sided P value of <0.05 was considered statistically significant.ResultsThe results were stratified by preterm status. Male preterm offspring of preeclamptic mothers had greater reductions in chest circumference, head circumference, and birthweight than preterm female offspring of preeclamptic women (P = 0.01, P = 0.02, and P = 0.05, respectively, for interaction). Female versus male preterm offspring exposed to preeclampsia were less susceptible to being small for gestational age (synergy index 0.38; 95% CI, 0.00–0.84). The influence of preeclampsia on the growth of term offspring was more modest, and the influence of sex was opposite that in preterm infants. Compared with term offspring of normotensive women, the reduction in mean ponderal index was greater for female versus term male offspring of preeclamptic women (P = 0.02, interaction).ConclusionFetal growth was more impaired among male versus female preterm infants born to preeclamptic women. Our study underlined the importance of incorporating sex differences in the study of biological mechanisms for immediate- and long-term consequences of suboptimal fetal growth.     

Alterations in KATP and KCa channel function in cerebral arteries of insulin-resistant rats

We examined whether insulin resistance alters the function of ATP-dependent and Ca(2+)-activated K(+) channels (K(ATP) and K(Ca) channels, respectively) in pressurized isolated middle cerebral arteries (MCAs) from fructose-fed insulin-resistant (IR) and control rats. Blockade of K(Ca) channels with tetraethylammonium chloride (TEA, 2.5 mM) or iberiotoxin (IBTX, 0.1 microM) increased the spontaneously developed tone in control MCAs by 10.5 +/- 1.3% (n = 10) and 13.3 +/- 2.3% (n = 6), respectively. In the IR arteries, TEA induced similar constrictions (8.0 +/- 1.1%, n = 10), but IBTX constricted the IR arteries by only 3.1 +/- 0.9% (n = 8; P < 0.01). Bradykinin (BK)-induced endothelium-mediated relaxation was reduced in IR MCAs. Maximum relaxation to BK (10(-6) M) was 42 +/- 4% in control (n = 9) and 19 +/- 2% in IR (n = 10; P < 0.01) arteries. Pretreatment with TEA, IBTX, or the K(ATP) channel blocker glibenclamide (10 microM) inhibited relaxation to BK in control MCAs but did not alter dilation in IR arteries. Relaxation to the K(ATP) channel opener cromakalim was also diminished in IR MCAs. Maximum relaxation to cromakalim (10(-5) M) was 48 +/- 3% in control (n = 6) and 19 +/- 2% in IR arteries (n = 6; P < 0.01). These findings demonstrate that insulin resistance alters the function of K(ATP) and K(Ca) channels in isolated MCAs and affects the control of resting vascular tone and the mediation of dilator stimuli.     

Higher de novo synthesized fatty acids and lower ω3- and ω6-long-chain polyunsaturated fatty acids in umbilical vessels of women with preeclampsia and high fish intakes

Umbilical veins (UV) and arteries (UA) of preeclamptic women in Curaçao harbor lower long-chain polyunsaturated fatty acids (LCP). The present aim was to test these findings in Mwanza (Tanzania), whose inhabitants have high LCPω3 and LCPω6 intakes from Lake Victoria fish. Women with preeclampsia (n=28) in Mwanza had lower PUFA and higher 20:0 in UV and UA, compared with normotensive/non-proteinuric controls (n=31). Their UV 22:6ω3, 22:4ω6, LCPω6, ω6, and LCPω3+ω6 were lower, while saturated FA, potentially de novo synthesized FA (Σde novo) and (Σde novo)/(LCPω3+ω6) ratio were higher. Their UA had higher 16:1ω7, ω7, 18:0, and 16:1ω7/16:0. Umbilical vessels in Mwanza had higher 22:6ω3, LCPω3, ω3, and 16:0, and lower 22:5ω6, 20:2ω6, 18:1ω9, and ω9, compared to those in Curaçao. Preeclampsia in both Mwanza and Curaçao is characterized by lower LCP and higher Σde novo. An explanation of this might be placental dysfunction, while the similarity of umbilical vessel FA-abnormalities in preeclamptic and diabetic pregnancies suggests insulin resistance as a common denominator.     

Coenzyme Q10 is increased in placenta and cord blood during preeclampsia

Preeclampsia is a common (approximately 7% of all pregnancies) disorder of pregnancy in which the normal hemodynamic response to pregnancy is compromised. Despite many years of intensive research, the pathogenesis of preeclampsia is still not fully understood. The objective of the present study was to investigate the levels of coenzyme Q(10) (CoQ(10)) in placental tissue compared to maternal and umbilical cord levels both during normal pregnancy and in those complicated with preeclampsia. Pregnant women (n = 30) and women with preeclampsia (n = 30) were included. Maternal, newborn cord blood levels and placental content of coenzyme Q(10) were measured by high performance liquid chromatography (HPLC). Plasma coenzyme Q(10) levels were significantly higher in normal pregnant women than in women with preeclampsia. CoQ(10) content in placenta from women with preeclampsia (mean 0.28 SEM 0.11 nmol/mg protein) was significantly higher compared to normal pregnancy (mean 0.09 SEM 0.01 nmol/mg protein; p = 0.05). Levels of CoQ(10) in cord blood from normal pregnant women (mean 0.30 SEM 0.05 micromol/l) were significantly lower than in preeclamptic women (mean 4.03 SEM 2.38 micromol/l). In conclusion, these data indicate a possible involvement of CoQ(10) in preeclampsia that might bear deep physiopathological significance and deserve to be further elucidated.     

Mesenteric vascular responsiveness in a rat model of pregnancy-induced hypertension

Reduced perfusion to the placenta in early pregnancy is believed to be the initiating factor in the development of preeclampsia, triggering local ischemia and systemic vascular hyperresponsiveness. This sequence of events creates a predisposition to the development of altered vascular function and hypertension. This study was designed to determine the influence of placental insufficiency on the responsiveness of mesenteric resistance arteries in an animal model of preeclampsia. Placental insufficiency was induced by reduction in uteroplacental perfusion pressure (RUPP) in experimental Sprague-Dawley rat dams. The uterine branches of the ovarian arteries and the abdominal aortae of pregnant rats were surgically constricted on gestational Day 14. Dams in the control group underwent a sham procedure. Rats were euthanized on gestational Day 20, followed by removal of the small intestine and adjacent mesentery. First-order mesenteric resistance arteries were mounted on a small vessel wire myograph and challenged with incremental concentrations of vasoconstrictors and vasorelaxants. Mesenteric arteries in dams with placental insufficiency demonstrated an increased maximal tension to phenylephrine (7.15 +/- 0.15 vs. 5.4 +/- 0.27 mN/mm, P < 0.001); potassium chloride at 60 mM (3.43 +/- 0.11 vs. 2.77 +/- 0.14 mN/mm, P < 0.01) and 120 mM (3.92 +/- 0.18 vs. 2.97 +/- 0.16 mN/mm, P < 0.01); and angiotensin II (2.59 +/- 0.42 vs. 1.51 +/- 0.22 mN/mm, P < 0.05). Maximal relaxation to endothelium-dependent relaxants acetylcholine and calcium ionophore (A23187) was not significantly reduced. Data suggest that placental insufficiency leads to hyperresponsiveness to vasoconstrictor stimuli in mesenteric arteries.