Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main clinical features of pre-eclampsia are oedema and vascular leakage. Cadherin-5 mediates endothelial cell-cell contact in the vascular endothelium and may regulate permeability as a vascular function. Therefore, we addressed the question of whether pre-eclampsia alters cadherin-5 expression and intracellular distribution. Confluent human umbilical vein endothelial cells (HUVEC) were incubated with 20% serum from patients with pre-eclampsia (n = 18), haemolysis-elevated liver enzymes-low platelet syndrome (HELLP) (n = 12), pregnancy-induced hypertension (PIH) (n = 18) or normal pregnancy (n = 10). After incubation with sera from patients with pre-eclampsia, immunostaining analyses showed cadherin-5 accumulation in vesicular and tubular structures of the Golgi apparatus. Immunoblot analyses of HUVEC after pre-eclampsia serum incubation showed an increase of the stable form of cadherin-5 while degradation products decreased. Degradation of cadherin-5 takes place at the cell membrane, so this decrease may be due to a decrease of cadherin-5 in the cell membrane. The accumulation of cadherin-5 in the vesicular and tubular structures of the Golgi apparatus indicates that targeting of cadherin-5 to the plasma membrane could be disrupted. We suggest that intracellular retention of cadherin-5 caused by serum factors in patients with pre-eclampsia may decrease the number of adhesion complexes in the cell membrane, thereby contributing to endothelial dysfunction.
Mol Hum Reprod 2000 Nov
PMID:Altered subcellular distribution of cadherin-5 in endothelial cells caused by the serum of pre-eclamptic patients. 1104 66

The presence of interleukin-15 (IL-15) mRNA in human placenta has been demonstrated previously. The present study was undertaken to investigate the expression profiles of IL-15 mRNA and protein in early and late gestational placental tissues, and also the effect of labour on its production. Levels of placental IL-15 expression were also determined in patients presenting with pre-eclampsia. An explant culture system was used to study the release of immunoreactive IL-15 by the placental tissues. Enzyme-linked immunosorbent assays were employed to quantify concentrations in the culture medium. The results showed that placental tissues from all groups released immunoreactive IL-15 into the culture medium. Moreover, the level of secretion by the term placental tissues was much higher than that by first trimester tissues. The presence of labour at term resulted in a further increase in placental IL-15 production. Reverse transcription-polymerase chain reaction (RT-PCR) was used to demonstrate the expression of IL-15 mRNA in these tissues. The results confirmed the expression of IL-15 in placenta from all the groups and the mRNA levels in the samples was highly correlated with the respective protein concentrations. Levels of both IL-15 mRNA and protein were significantly reduced in the pre-eclamptic placental tissue compared with the normal controls. The present study suggests an important role for this novel cytokine in human pregnancy.
Mol Hum Reprod 2001 Jan
PMID:Expression profiles of interleukin-15 in early and late gestational human placenta and in pre-eclamptic placenta. 1113 66

Extensive angiogenesis and invasion of the maternal decidua by trophoblasts are essential for the development and function of the placenta. Vascular endothelial growth factors (VEGF), placenta growth factor (PlGF) and their receptors VEGFR-1/Flt-1, VEGFR-2/KDR and VEGFR-3/Flt4 have important roles in vasculogenesis and angiogenesis. We have studied the localization of these proteins by immunohistochemistry and Western blotting in the placenta and of PlGF in maternal serum, and their association with diabetes, pre-eclampsia, fetal growth restriction (FGR) and fetal alcohol syndrome (FAS). VEGFR-1 and VEGFR-3 were detected mainly in the syncytiotrophoblastic layer whereas VEGFR-2 was detected in the vascular endothelial cells of the placenta. VEGFR-1, but not the other receptors, showed increased expression in placental syncytiotrophoblasts from 50% of patients with severe pre-eclampsia and FGR when compared with normal placentas. PlGF was undetectable in 38 of 44 samples of amniotic fluid of mothers with normal and complicated pregnancies. However, maternal serum PlGF concentrations were significantly lower in pre-eclamptic patients and in those with FGR when compared to diabetic women or healthy controls. These results suggest that low maternal serum PlGF and increased placental expression of its receptor VEGFR-1 are associated with pre-eclampsia and FGR.
Mol Hum Reprod 2001 Feb
PMID:Expression of vascular endothelial growth factor receptors 1, 2 and 3 in placentas from normal and complicated pregnancies. 1116 Aug 48

We have studied the cellular localization of the relaxin-like factor (RLF) in the histologically normal cyclic endometrium collected from days 3--26 of the menstrual cycle. RLF transcripts and protein were detected in the luminal and glandular epithelium and in stromal cells at all stages of the cyclic endometrium. Increased expression of RLF was observed in endometrial tissues in the proliferative as compared to the secretory phase, suggesting that oestrogens affect RLF gene activity in the human endometrium. The cellular localization of RLF transcripts and protein was also determined in first trimester placental tissues obtained from normal and ectopic tubal implantation sites and in third trimester placentae of normal and pre-eclamptic pregnancies. In first trimester placenta, weaker expression of RLF was observed in the syncytiotrophoblast as compared to the underlying cytotrophoblast. Extravillous trophoblast cells constitutively expressed RLF. Trophoblast cells were the main source of RLF in the human placenta and trophoblastic RLF gene activity was unaffected by either the site of implantation or the invasive properties of the cytotrophoblast as demonstrated by samples from patients with tubal implantation and pre-eclampsia respectively. Decidual cells weakly expressed RLF. The presence of unprocessed and cleaved immunoreactive RLF in term placenta was determined by Western analysis. The above results suggest a functional role for both RLF isoforms within normal placental tissue.
Mol Hum Reprod 2001 Apr
PMID:Cellular localization of human relaxin-like factor in the cyclic endometrium and placenta. 1127 97

Inhibin-related proteins are involved in the control of the feto-maternal communication required to maintain pregnancy. Human placenta, decidua, and fetal membranes are the major sites of production and secretion of activin A, inhibin A and inhibin B in maternal serum, amniotic fluid, and cord blood. The availability of suitable assays developed in the last years has enabled the measurement of inhibins and activin A in their dimeric forms, in order to investigate their role in physiological conditions of pregnancy. The studies conducted on inhibin-related proteins and human pregnancy suggested the possibility of an involvement of inhibin A and activin A in the pathogenesis of gestational diseases. In fact, several lines of evidence underline the potential role and the clinical usefulness of inhibin-related proteins measurement in the diagnosis, prevention, prognosis and follow-up of different gestational pathologies such as early pregnancy viability, Down's syndrome, fetal demise, pre-eclampsia, pregnancy-induced hypertension, preterm delivery and intrauterine growth restriction. The measurement of inhibin A and activin A into the biological fluids of pregnancy will offer in the future, further possibilities in the early diagnosis, prediction, and monitoring diseases of pregnancy.
Mol Cell Endocrinol 2001 Jun 30
PMID:Changes in inhibins and activin secretion in healthy and pathological pregnancies. 1145 81

Unexplained fetal death in utero in late pregnancy represents an increasing proportion of perinatal deaths. It has been assumed that critical hypoxia is the likely mechanism underlying these losses, but the lack of a physiological marker has hampered both confirmation and prediction which could lead to timely intervention. In this paper, we report studies on hypoxia that we have performed in chronically cannulated late pregnant sheep, complemented by parallel investigations undertaken in human pregnancies. Our initial studies were directed towards determining activin secretion in the fetus and mother during late gestation, and immediately after fetal surgery using a sheep model. This led us to propose that there may be a relationship between hypoxia and activin A, follistatin and prostaglandin (PG) release from the feto-placental unit. Subsequent studies have been directed towards examining this potential relationship in sheep and in humans with compromised pregnancies. As a result of these studies, we have identified a potential mechanism by which activin A may be involved in regulating the response of the fetus to hypoxic insult. Activin A and follistatin concentrations increased in late gestation in ovine maternal plasma and in fetal fluids. Feto-placental hypoxemia or maternal isocapnic hypoxemia, leading to fetal hypoxia, were specific triggers for an acute increase in fetal activin A and follistatin concentrations during late gestation. The source and secretion of activin A, follistatin, and the associated release of PGE(2,) from within the feto-placental unit varied according to the site of the insult. The concomitant secretion of activin A and PGE(2) into the fetal circulation and amniotic fluid during reduced uterine blood flow provides an insight into the physiological regulatory mechanisms that might be involved. Changes observed in maternal activin A concentrations in mid and late gestation in the human may also be associated with fetal compromise. In human pregnancies, elevated activin A concentrations were observed in maternal plasma in mid and late gestation, in association with severe pre-eclampsia and with severe fetal growth restriction, compared to those observed in pregnancies with constitutionally small, healthy fetuses. Activin A was also elevated in maternal and arterial cord plasma in women at term during labour and immediately prior to undergoing emergency Caesarean section for failure to progress. These findings offer exciting new possibilities to gain insights into the mechanisms that underlie the maintenance of fetal wellbeing and provide a rationale for the potential that activin A may prove to be a useful clinical marker of fetal distress.
Mol Cell Endocrinol 2001 Jun 30
PMID:Physiological and regulatory roles of activin A in late pregnancy. 1145 82

Altered placental and circulating levels of vascular endothelial growth factor (VEGF) and its receptor (flt-1) may be associated with pre-eclampsia and intrauterine growth restriction (IUGR). The aim of this study was to determine whether chorionic villous VEGF or flt-1 mRNA are altered at early gestation in pregnancies subsequently found to be complicated by abnormal fetal growth. Quantitative reverse transcription-polymerase chain reaction was performed on chorionic villous samples for VEGF and flt-1 using an internal RNA standard. Using the individualized birthweight ratio (IBR), the subjects (n = 51) were divided into three groups; IUGR (IBR <10th centile, n = 6), normal (IBR 10th-90th centiles, n = 41) and macrosomic (IBR >90th centile, n = 4). There was no correlation between the mRNA expression of VEGF(121) or VEGF(165) and gestational age of the normal controls. There was also no difference in the expression of either of the VEGF isoforms between the IUGR or macrosomic groups and the normal controls. Expression of flt-1 was below the detection limit of the assay. In conclusion, we have found that altered chorionic villous expression of VEGF is not associated with the initial stages of development of IUGR or macrosomia.
Mol Hum Reprod 2001 Nov
PMID:Abnormal fetal growth is not associated with altered chorionic villous expression of vascular endothelial growth factor mRNA. 1167 77

The human placenta has been considered to possess a locally generated renin-angiotensin system (RAS), which may play a physiological role in the regulation of uteroplacental blood circulation. The changes in the expression of such a placental RAS during pregnancy could be important for the physiological and pathophysiological aspects of some clinical disorders, such as pregnancy-induced hypertension, preeclampsia. In the present study, the alterations of expression and localization of placental angiotensin II receptor subtypes, namely AT(1) in patients with preeclampsia (elective caesarean delivery) were investigated and compared with controls (vaginal delivery and elective caesarian delivery) using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blot and immunohistochemistry respectively. Results from RT-PCR analysis revealed an upregulated expression of placental mRNA for AT(1) receptor subtype in patients with preeclampsia when compared with those in controls. In addition, there was also a significant activation of placental expression of angiotensinogen mRNA in patients with preeclampsia. Results from Western blot showed that the expression of AT(1) receptor was also upregulated. Immunohistochemical results further demonstrated that increased immunoreactivity for placental AT(1) receptor was predominantly localized to the thin layers of syncytiotrophoblasts and, to a less extent, the capillaries of the term placental villi. These data indicate that upregulation of placental RAS components, notably AT(1) receptor in the syncytiotrophoblasts, could play a pathophysiological role in patients with preeclampsia.
Mol Cell Endocrinol 2001 Nov 26
PMID:The upregulation of angiotensin II receptor AT(1) in human preeclamptic placenta. 1169 45

Pre-eclampsia is a disorder of human pregnancy occurring in 5-10% of all births, and represents the leading cause of infant morbidity and mortality and maternal death. In pre-eclampsia, invasion of fetal trophoblasts into maternal arteries during early pregnancy is shallow or absent. Here we examined the hypothesis that HLA-G, a non-classical class I HLA expressed in cytotrophoblasts, may act as a key gene in pre-eclampsia. We analysed HLA-G at the level of transcription and genotyped a silent CAC-CAT polymorphism in exon 3 and a 14-bp insertion/deletion in the 3' untranslated region. A deficit in levels of the HLA-G3 transcript was observed in mild pre-eclampsia compared to normal placentas. The distribution of HLA-G polymorphisms was different between normal and pre-eclampsia samples. A correlation between the alteration in transcription of the HLA-G gene and certain HLA-G genotypes was also observed. Thus we provide the first evidence for a possible role of HLA-G in genetic susceptibility to, and pathogenesis of pre-eclampsia.
Cell Mol Life Sci 2001 Nov
PMID:Altered HLA-G transcription in pre-eclampsia is associated with allele specific inheritance: possible role of the HLA-G gene in susceptibility to the disease. 1176 89

We determined the serum levels of leptin in 96 pregnant women with body mass index between 20 to 30, 30 normal (NP), 26 with mild preeclampsia (MPE), 27 with severe preeclampsia (SPE), 6 with chronic hypertension plus preeclampsia (CHT+PE) and 7 with chronic hypertension (CHT). A significant (p < 0.01) decrease in leptin levels was observed in the SPE group when compared with the NP group. On the contrary, significant (p < 0.05) increases were observed in the CHT and CHT+PE groups when compared with the NP group. Leptin levels were significantly higher in the MPE (p < 0.001), CHT (p < 0.01) and CHT+PE (p < 0.5) groups when compared with the SPE. No significant differences were observed in the CHT group when compared with CHT+PE. Moreover, a positive correlation was encountered (r = 0.6, p < 0.001) between platelet number and leptin levels for all the patients with preeclampsia. These results suggest that leptin levels may be useful metabolic parameter in different types of hypertension during pregnancy.
Res Commun Mol Pathol Pharmacol 2000
PMID:Serum leptin levels in different types of hypertension during pregnancy. 1191 7


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