Preeclampsia is the major cause of maternofetal and neonatal morbi-mortality including intrauterine growth retardation, miscarriages and stillbirths. Inadequate vascular dilation and angiogenesis represent the crucial underlying defect of gravidic hypertension, denoting a failed response to the vasodilatory and pro-angiogenic challenge imposed by pregnancy, especially if multifetal. A similar pathogenesis appears involved in gestational diabetes. In this review we aimed to provide a hint on understanding the deeply involved angiogenic disorders which eventually culminate in utero-placental failure. The key players in these complex processes may be found in an intricate network of growth factors (GFs) and GF inhibitors, controlled by several vascular risk factors modulated by environment and genes, which eventually impact on early and late cardiovascular outcomes of mother and fetus. 相似文献
Although a number of studies have measured circulating levels of some trace elements in preeclampsia (PE) and compared to healthy pregnant (HP), there is no consensus yet about the deficiency of some metals and development of hypertensive disorders in pregnancy. The aim of this study was to compare plasmatic levels of Zn, Mn, Co, Cu, Se and Sr among non-pregnant (NP), healthy pregnant (HP), gestational hypertensive (GH) and preeclamptic (PE) women and to correlate these levels with plasma soluble endoglin (sENG) and soluble fms-like tyrosine kinase-1 (sFLT-1), two important antiangiogenic proteins related to PE. A total of 184 women were enrolled in this study (NP = 35, GH = 51, PE = 37 and HP = 61). Trace element analyses were carried out with an inductively coupled plasma mass spectrometer (ICPMS). sENG and sFLT-1 plasma concentrations were measured by commercial ELISA kits. The most interesting result is that Sr is higher in PE (63%, P < 0.001) compared to HP and their levels are positively correlated with sENG in all three groups of pregnant women. Moreover, we found a negative correlation between Zn and sENG in HP (r = −0.43, P = 0.003). Regarding other elements, we found similar levels among pregnant groups. In conclusion, this study showed that Sr may has a role in physiopathology of PE. 相似文献
Background: Preeclampsia, a pregnancy disorder characterized by hypertension and proteinuria, represents the leading cause of fetal and maternal morbidity and mortality in developing countries. The identification of novel and accurate biomarkers that are predictive of preeclampsia is necessary to improve the prognosis of patients with preeclampsia.
Objective: The objective of this study is to evaluate the usefulness of nine urinary metalloproteinases to predict the risk of preeclampsia development.
Methods: MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12 and MMP-13 were analyzed in urine (early-pregnancy) from 17 women predicted to develop preeclampsia and 48 controls using the Bio-Plex Pro-Human MMP panel (Bio-Rad, Hercules, CA).
Results: Urinary MMP-2 showed differences between groups which allowed us to calculate an increased risk for PE development of up to 20 times among the study population.
Conclusion: Increased urinary concentration of MMP-2 at 12 and 16 weeks of gestation predicted an increased risk of developing preeclampsia in the study population. 相似文献
Notch proteins are a transmembrane receptor family that is structurally and functionally conserved from worms to humans. The
mammalian family of Notch proteins consists of several genes encoding Notch receptors and related Notch ligands. Notch signaling
is involved in different aspects of the cell-fate decision tree: differentiation, proliferation, and apoptosis. These three
processes are finely regulated in human placenta in order to allow a successful pregnancy and correct fetal growth. Notch
and its ligands also participate in vascular remodeling and stabilization. Vasculogenesis and blood regulation are of importance
in the human placenta for normal fetal development and growth; any disorder of these systems leads to preeclampsia. Drawing
on this background, we have investigated the expression of Notch-1, Notch-4, and Jagged-1, together with two members related
to the Notch pathway in angiogenesis: VEGF and p21. Normal and preeclamptic human placentas have been evaluated by immunohistochemistry.
In preeclamptic samples, a down-regulation of Notch pathway members occurs with a weak/moderate expression of the Notch protein
members in all components of placenta compared with physiological placentas that, at term, exhibit the strong expression of
Jagged-1 and a moderate expression of both Notch-1 and Notch-4 in all compartments of the placental villi. Moreover, preeclamptic
samples also reveal a down-regulation of VEGF expression, together with a moderate nuclear expression of p21Cip1 in the syncytiotrophoblast, cytotrophoblast, and endothelial cells. This down-regulation of VEGF in preeclamptic placentas,
in turn, probably decreases Notch protein expression in placental compartments and in endothelial cells and could offer an
ethiopathogenetic explanation for the onset of this pathology. 相似文献
The maternal-fetal interface, a chimeric structure, is formed when fetal cytotrophoblasts (CTBs) from the placenta invade
the uterine wall and its resident vasculature. In preeclampsia (PE), interstitial and endovascular invasion are often shallow,
and fewer spiral arterioles are breached in toto. Our previous work has shown that faulty CTB differentiation to an invasive
phenotype is a contributing factor. Here, we have tested the hypothesis that the constellation of morphological and molecular
defects that are associated with PE are unique to this condition. Specifically, we have compared the histology of the maternal-fetal
interface and CTB expression of stage-specific antigens in PE and in preterm labor (PTL) with or without inflammation. In
the absence of inflammation, biopsies obtained after PTL were near normal at histological and molecular levels. In accord
with previously published data, PE had severe negative effects on the endpoints analyzed. Biopsies obtained after PTL with
inflammation had an intermediate phenotype. Our results suggest that the maternal-fetal interface from cases of PTL without
inflammation can be used for comparative purposes, e.g., as age-matched controls, in studies of the effects of PE on cells
in this region.
This work was supported by the Intramural Division of NICHD (Perinatology Research Branch) and HD 30367. 相似文献
The objective of this study was to determine the concentration of free
-amino acids and in particular of
-arginine in the plasma of pregnant women affected by preeclampsia compared to healthy pregnant women in order to know if an alteration in the concentrations of these amino acids occurs in preeclamspia. Twelve pregnant women affected by preeclampsia and twelve pregnant control women, ages 28–35 years old and at the 35–36 weeks of pregnancy were studied. The blood analysis of free amino acids was carried out by using a high performance liquid chromatographic (HPLC) fluorometric method and OPA-NAC as derivatizing agent for the amino acid determination. In the blood of women affected by preeclampsia
-arginine is markedly reduced compared to controls (about five-fold lower, P<0.01). The other amino acids also are significantly reduced, but to lesser extents (about 1.5 times lower, P<0.05). Thus, the determination of
-arginine in the blood of pregnant women could potentially constitute an additional marker for the early diagnosis of preeclampsia. 相似文献