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1.
Objective: We have recently demonstrated that matrix metalloproteinase-2 (MMP-2) alters vascular function through cleavage of vasoactive peptides, resulting in increased vasoconstriction and reduced vasodilation. We, therefore, hypothesized that MMP levels are increased in women with preeclampsia. In addition, because vascular endothelial growth factor (VEGF) has been implicated in the pathophysiology of preeclampsia and is involved in angiogenesis that requires the release of proteases to allow for migration of endothelial cells, we hypothesized that VEGF increases release of MMPs from endothelial cells. Methods: We used zymographic analysis to evaluate MMP-2/MMP-9 levels in plasma of women with preeclampsia ( n=12) compared to women with uncomplicated pregnancies ( n=12). In addition, we evaluated the changes in the levels of MMP-2 and MMP-9 as well as tissue inhibitors of MMPs (TIMP-1 and TIMP-2) released by cultured human umbilical vein endothelial cells in response to VEGF (0.1–10 ng/mL). Results: Our data showed that plasma MMP-2 levels were significantly higher in women with preeclampsia compared to women with uncomplicated pregnancies (arbitrary intensity units: 690 ±111 and 252 ±56, respectively, p<0.05). MMP-9 levels were below the level of detection. In addition, VEGF stimulated endothelial MMP-2 and MMP-9 release in a concentration- and time-dependent (6–24 h) manner. Moreover, VEGF stimulation of MMP release occurs without significantly affecting the release of TIMP-1 and TIMP-2. Conclusions: These data suggest that VEGF promotes secretion of MMPs from endothelial cells that, in turn, could alter vascular function in women with preeclampsia. 相似文献
3.
Objective. To determine what threshold for proteinuria could best predict clinical outcome and whether this threshold could be applied universally to any biochemical assay. Design. A prospective observational study of hypertensive pregnancies referred for further assessment after in a UK University hospital (n = 197). Twenty-four hour urine protein was measured by two different assays [benzethonium chloride assay (BCA) and Bradford assay]. The differences between the two assays were calculated from Receiver Operating Characteristic (ROC) curves. Commonly used thresholds for defining preeclampsia (0.3 and 0.5 g/24 hours) were explored for both assays for the prediction of adverse clinical outcomes (severe hypertension, Birthweight < 10th percentile, preterm delivery, and a composite biochemical/haematological derangement). Results. The two assays are not equivalent. The prevalence of > 300 mg/24 hour proteinuria and, hence, the prevalence of preeclampsia differed between the two assays. ROC curve analysis demonstrates that the two assays are similar in terms of overall performance as predictive tests. However the threshold of 300 mg/24 hours performs poorly as a predictor of clinical risk. Likelihood ratios (LR) for the BCA at the 300 mg/L threshold for each clinical outcome do not achieve statistical significance. At the 500 mg/L threshold, the LR + for the BCA assay does achieve statistical significance for severe hypertension (LR + : 1.51 95% CI 0.99–2.28) and for birthweight < 10th percentile (LR + : 1.72 95% CI 1.11–2.66). For the Bradford assay at the 300 mg/24 hour threshold, the LR + does achieve statistical significance for birthweight < 10th percentile (LR + : 1.71 95% CI 1.41–4.31). However, at the 500 mg/24 hour threshold, the LR + is significant for severe hypertension (LR + : 2.15 95% CI 1.07–4.34), birthweight < 10th percentile (LR + : 2.79 95% CI 1.4–5.54) and biochemical disease (LR + : 2.47 95% CI 1.22–5.01). Conclusions. This study suggests that thresholds for proteinuria need to be higher (possibly ≥ 0.5 g/24 hours) and there is the need for a “gold standard” proteinuria assay against which all other measures of quantification can be assessed. 相似文献
4.
Objectives: To evaluate the circulating levels of antibodies to oxidized low-density lipoprotein (LDL) and their correlation with the lipid peroxide/vitamin E ratio in pregnant women with preeclampsia and chronic hypertension. Methods: Antibodies to oxidized LDL were measured by enzyme-linked immunoassay, lipid peroxides (malondialdehyde), and vitamin E were measured by high-pressure liquid chromatography. Patients were 25 healthy pregnant women, 20 previously nonhypertensive women diagnosed with preeclampsia, and 20 women with uncomplicated chronic hypertension. Results: Serum levels of antibodies to LDL in preeclamptic patients were similar to controls, whereas women with chronic hypertension showed a trend for increased mean levels. Lipid peroxides in serum were significantly increased and vitamin E levels were significantly decreased in preeclampsia with respect to nonhypertensive pregnancy, but no differences were observed for chronic hypertensive women. Conclusions: Our results suggest that preeclampsia is not accompanied by increased levels of antibodies to oxidized LDL. By contrast, and according to previous studies in nonpregnant patients, chronic hypertensive patients showed a trend for elevated levels. 相似文献
5.
OBJECTIVE: This study investigated the association among the inducible 70-kd heat shock protein, cytokines, and microbial flora in the vagina in mid trimester pregnant women and subsequent preterm delivery. STUDY DESIGN: Vaginal samples from 205 pregnant women, which were collected at 18 to 22 weeks of gestation, were analyzed for qualitative and quantitative vaginal microflora and for 70-kd heat shock protein, interleukin-1beta, interleukin-1 receptor antagonist, and tumor necrosis factor-alpha by enzyme-linked immunosorbent assay. Pregnancy outcome data were obtained subsequently. RESULTS: The 70-kd heat shock protein was detected in 38 vaginal samples (18.5%). Its presence was associated with elevated vaginal pH, a diagnosis of bacterial vaginosis, and elevated interleukin-1 receptor antagonist levels (P < .001). Among women with bacterial vaginosis, 70-kd heat shock protein-positive subjects had a >80% increase in median vaginal concentration of interleukin-1 receptor antagonist (P < .05). CONCLUSION: Vaginal 70-kd heat shock protein expression is associated with the down-regulation of the proinflammatory immune response to abnormal vaginal flora in mid trimester pregnant women. 相似文献
6.
Objective: To determine international expert practice of fluid management and monitoring in severe preeclampsia. Methods: The 447 members of the ISSHP (International Society for the Study of Hypertension in Pregnancy) were issued a postal questionnaire to determine their views and practices of fluid management in severe preeclampsia. Results: One hundred sixty-six (37%) completed questionnaires were received. Responses indicated that there is no consensus regarding most aspects of management of severe preeclamptic patients. In particular, there is no agreement about which fluid type to administer and how to assess circulatory status in these patients. There were also wide variations in the use of plasma volume expansion as a treatment modality. Statistical comparison of the use of Swan–Ganz catheters in “theoretical” and “actual” practice showed highly significant differences ( p < 0.001). The majority of respondents were interested in participating in future research. Conclusion: The results reflect genuine uncertainty generated by a lack of evidence from randomized trials addressing the acute management of severe preeclamptic patients. Even where clinicians are confident “in theory” that a particular form of treatment is the best, they do not appear to have the resources or commitment to match this with “practice.” The majority of respondents were very keen to develop the questions raised further in the context of multicenter clinical trials. 相似文献
7.
Objective: Red blood cell (RBC) deformability is one of the factors determining microcirculation. In preeclampsia (PE) and some cases of intrauterine growth restriction (IUGR), microcirculation appears to be reduced. The aim of the study is to examine whether there are differences in RBC deformability in uncomplicated pregnancy when compared to pregnancies complicated by PE and/or IUGR. Material and methods: RBC deformability of 87 pregnant women with initially normal pregnancies was evaluated with the laser diffractoscope. RBC deformability was measured beginning in week 16 of gestation up to 5 days after delivery. Thirty-seven women had an uncomplicated pregnancy. In addition, RBC deformability of 10 nonpregnant women was measured on days 5 and 22 of their menstrual cycle. RBC deformability of women with preeclampsia (PE, N=15), intrauterine growth restriction (IUGR, N=17), or PE plus IUGR ( N=17) was measured weekly, beginning with the onset of clinical symptoms, up to 5 days after delivery. Results: In early uncomplicated pregnancies, RBC deformability does not differ from the nonpregnant state. At week 30 of gestation, there is a slight decrease in RBC deformability followed by a return back to the values of nonpregnant women after delivery. Women with PE and/or IUGR show reduced RBC deformability. This is most pronounced in cases with severe fetal or maternal complications. After delivery, RBC deformability also returns to nonpregnancy values within 5 days. Conclusion: Reduced RBC deformability may contribute to a reduced microcirculation in PE and IUGR. Increasing RBC deformability therapeutically in these cases could offer new options for the treatment of decreased uterine and fetal perfusion and their sequelae. 相似文献
8.
AimTo evaluate the possible association of three different HSP70 gene polymorphisms with preeclampsia. Study designHSPA1A G(190)C, HSPA1B A(1267)G and HSPA1L T(2437)C polymorphisms were analyzed from blood samples of 72 women with preeclampsia and of 70 healthy pregnant women as controls by PCR-RFLP method. ResultsHSPA1B (1267)GG and HSPA1L (2437)CC genotypes occurred more frequently in preeclamptic patients compared to healthy controls ( p < 0.002 [RR: 4.38, 95% CI: 1.56–12.28]) and ( p < 0.03 [RR: 1.31, 95% CI: 1.03–1.67]), respectively. Significant difference was found in the distribution of HSPA1B A(1267)G genotype between the preeclamptic and control group ( p < 0.004 [RR: 0.67, 95% CI: 0.51–0.88]). Distribution of HSPA1A G(190)C was similar in the preeclamptic and control group. In controls, genotype distribution of HSPA1A G(190)C and HSPA1L T(2437)C was in Hardy–Weinberg equilibrium, while this criterion was not fulfilled for HSPA1B A(1267)G. ConclusionWe concluded that HSPA1B (1267)GG and HSPA1L (2437)CC genotypes were more frequent among preeclamptic than control patients, suggesting that these genotypes may play a role in the susceptibility for preeclampsia. 相似文献
9.
目的:进一步阐明胎盘血管病(PVD)的发病机制.方法:选取胎盘血管病组(研究组)与正常孕妇(对照组)两组标本,选择应用寡核苷酸芯片技术筛选出差异表达水平较高的基因,定量PCR和Western-blot验证表达,并应用免疫组化检测定位.结果:与对照组相比,Hsp A1A和HspA6表达水平显著改变,且共同编码热休克蛋白(Hsp 70);Hsp 70在胎盘微血管中主要表达在内皮细胞和平滑肌细胞;研究组与对照组相比,Hsp 70 mRNA和蛋白的表达均增高(P<0.05);Hsp 70 mRNA和蛋白的表达均与胎儿出生时的体重呈负相关(P<0.05).结论:Hsp 70在PVD的发病机制中是极其重要的,Hsp 70高表达可能引起了内在的免疫应答和炎性反应. 相似文献
10.
AbstractDiabetes mellitus (DM) is associated with an increased risk of endometrial carcinoma (EC). Heat shock proteins have a role in the modulation of both diseases. The aim of this study was to investigate extracellular HSP70 (eHSP70) level alternations in patients with two different types of EC (endometrioid and non-endometrioid) with and without type 2 diabetes. In a case–control study, 88 participants were enrolled in four groups including: 18 EC patients with DM, 19 EC patients without DM, 29 patients with DM, and 22 healthy individuals. Blood samples were taken before surgery in cancer patients. Estradiol, eHSP70, sex hormone-binding globulin (SHBG), FBS, and HbA1c were assessed. Serum HSP70 level was higher in patients with diabetes (52.24?±?14.2?ng/ml) compared to healthy controls (39.04?±?6.96) ( p?<?.05). It was lower in EC (26.05?±?12.28) compared to healthy controls (39.04?±?6.96) ( p?<?.05). eHSP70 was also lower in endometrioid-type carcinoma (22.57?±?11) compared to non-endometrioid type (31.55?±?12.38) ( p?<?.05). Further analysis showed increased levels of eHSP70 in patients having both endometrioid-type carcinoma and diabetes (27.23?±?11.41) compared to the same patients without DM (17.08?±?7.78) ( p?<?.05). Presence of diabetes in patients with endometrioid type carcinoma resulted in an increase in eHSP70 approaching the level of eHSP70 in patients with non-endometrioid histology. 相似文献
11.
目的:探讨热休克蛋白70(HSP70)的表达与自发性早产合并组织学绒毛膜羊膜炎(HCA)的关系。方法:选择2015年6月至2016年1月在郑州大学第三附属医院产科住院并分娩的早产临产孕妇46例为早产临产组,并随机选择同期足月正常分娩的孕妇31例(足月正常组)为对照组。早产临产组孕妇根据分娩后胎膜组织病理学检查结果,分为早产合并HCA组(21例)及早产未合并HCA组(25例)。ELISA法测定并比较各组孕妇外周血、脐血中HSP70蛋白水平,采用免疫组化SP法、Western blotting法及RT-PCR法检测并比较各组孕妇胎膜组织中HSP70蛋白及mRNA的表达水平。采用Pearson相关分析法分析各组HSP70蛋白的相关性。结果:(1)早产合并HCA组孕妇外周血、脐血及胎膜组织中HSP70蛋白的表达和胎膜组织中HSP70 mRNA的表达高于早产未合并HCA组,早产临产组均高于足月正常组,3组间两两比较,差异均有统计学意义(P0.01)。(2)早产合并HCA组中孕妇外周血与脐血及胎膜组织中HSP70蛋白的表达均呈正相关(P0.05)。(3)早产合并HCA组中新生儿败血症发生率高于其余两组(P0.05)。结论:HSP70在早产及其合并HCA时表达增加,HSP70可能参与了早产的发生机制,同时与HCA及新生儿败血症有关。 相似文献
12.
Objective: To examine the expression of the heat shock protein hsp70-2, and the possible relationship with the pathogenesis of male infertility. Design: Prospective study. Setting: Reproductive testing laboratory in a university hospital. Patient(s): Men undergoing testicular biopsy during an investigation of subfertility. Intervention(s): Testicular tissues were obtained from biopsies of men undergoing infertility evaluation and subdivided into three groups: normal testes, maturational arrest and Sertoli cell-only syndrome. Immunostaining and Western blotting techniques determined expression of the heat shock protein hsp70-2 Main Outcome Measure(s): Expression of the heat shock protein hsp70-2 in the testes. Result(s): The experimental data demonstrated that the heat shock protein hsp70-2 was expressed in the normal and maturation arrest testicular specimens. The heat shock protein hsp70-2 was strongly present in the cytoplasm of spermatocytes and spermatides in the adluminal compartment of the seminiferous epithelium in normal testis. However, maturation arrest testis tissue demonstrated light staining in spermatocytes and spermatides, and Sertoli-only specimens demonstrated no staining for the heat shock protein hsp70-2. The Western blotting data showed a 70-kDa heat shock protein in the normal and maturation arrest testicular tissues, but not in the Sertoli-only tissues. Conclusions: These results suggest that the heat shock protein hsp70-2 is expressed in spermatocytes and spermatides in normal and maturation arrest tissues. However, the expression of the heat shock protein hsp70-2 was low in maturation arrest, and no heat shock protein hsp70-2 was demonstrated in Sertoli-only specimens. Therefore the decreased expression of the heat shock protein hsp70-2 is associated with the pathogenesis of male infertility. 相似文献
13.
AIM: The aim of this study was to investigate heat-shock protein (Hsp)70 as a novel marker to evaluate the curative effects of treatment for preterm delivery high-risk patients and pre-eclampsia. METHODS: After obtaining informed consent, serum samples were collected from 31 preterm delivery high-risk patients with a tocolysis index of three points or above (A), seven pre-eclampsia patients (P), 46 normal pregnant women (B), and seven non-pregnant women (C). Of the 31 preterm delivery high-risk patients, 15 had preterm delivery (Ap) and 16 had full-term delivery (Af). The levels of Hsp70 were measured using enzyme-linked immunosorbent assay. RESULTS: The Hsp70 levels in normal pregnant women were 8.6 +/- 1.9 ng/mL (first trimester), 5.5 +/- 1.0 ng/mL (second trimester) and 5.5 +/- 0.7 ng/mL (third trimester). There was no statistical difference in the Hsp70 levels between the three trimesters. The mean Hsp70 levels were 21.9 +/- 5.3 ng/mL (A), 35.3 +/- 9.6 ng/mL (Ap), 9.4 +/- 2.2 ng/mL (Af), 24.4 +/- 3.6 ng/mL (P), 6.1 +/- 0.6 ng/mL (B), and 2.4 +/- 0.6 ng/mL (C). Group Ap had significantly higher Hsp70 levels than group Af (P = 0.0112) and group B (P <0.0001). The duration of pregnancy after hospitalization for group Ap was significantly shorter than that for group Af (P=0.0088) and group B (P <0.0001). Group P also had significantly higher Hsp70 levels than group B (P <0.0001). CONCLUSION: Because Hsp70 levels were particularly high in treatment-resistant preterm delivery cases, Hsp70 may prove to be a useful marker for evaluating the curative effects of treatment for preterm delivery. 相似文献
14.
OBJECTIVE: We have recently demonstrated that serum 70 kDa heat shock protein (Hsp70) levels are increased in the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome). The aim of the present study was to investigate in an independent, larger cohort of patients whether serum Hsp70 levels are related to laboratory markers of HELLP syndrome. STUDY DESIGN: The study population included 14 patients with HELLP syndrome. Serum Hsp70 levels were measured by enzyme-linked immunosorbent assay. The relationship between serum Hsp70 levels and laboratory markers of hemolysis, hepatocellular damage, renal insufficiency, inflammation or disseminated intravascular coagulation (DIC), as well as platelet count was investigated by calculating correlation coefficients, standardized regression coefficients and by principal component analysis. RESULTS: Serum Hsp70 levels showed a very strong correlation to the markers of hemolysis (plasma free hemoglobin level, serum lactate dehydrogenase activity, and total bilirubin level) and of hepatocellular injury (serum aminotransferase activities), supported also by principal component analysis. Furthermore, circulating Hsp70 concentration reflected the severity of HELLP syndrome as expressed by the significant inverse correlation to the lowest platelet count. By contrast, there was no relationship between serum Hsp70 levels and markers of inflammation, coagulation, fibrinolysis or renal insufficiency. CONCLUSION: Elevated serum 70 kDa heat shock protein level seems to reflect tissue damage (hemolysis and hepatocellular injury) and disease severity in patients with HELLP syndrome. However, further investigations are needed to determine the clinical relevance of these findings. 相似文献
15.
Objective: Endothelial dysfunction is associated with increased oxidative stress in the vascular system in women with preeclampsia (PE), a hypertensive disorder occurring during human pregnancy. However, due to the nature of the disease, direct evidence of increased endothelial oxidative stress in the maternal vascular system at an in vivo situation is still lacking. We previously reported that primary cultured endothelial cells (ECs) from umbilical cords (HUVECs) from pregnancies complicated by PE exhibit phenotypic changes compared to those from normal pregnancies such as reduced eNOs expression associated with disorganized endothelial junction protein distribution and increased endothelial permeability. In this study, we sought to determine whether increased oxidative stress was also present in primary cultured HUVECs from women with PE. Methods: HUVECs were isolated from normal and PE pregnancies and EC oxidative stress was examined by superoxide generation using positive nuclear dihydroethidium (DHE) staining as an indicator. Since Hsp90 is believed to have protective effects on endothelial function, we also determined mRNA and protein expression for Hsp90. Using Hsp90 inhibitor geldanamycin (GA), we further determined the potential role of Hsp90 in superoxide generation, eNOs expression, and prostacyclin production of altered EC function associated with PE pregnancies. Results: We found that primary cultured ECs from PE pregnancies showed an increase in DHE positive cells, p < 0.01. Hsp90 protein expression was significantly decreased in ECs from PE compared with that from normal pregnancies, p < 0.05. Inhibition of Hsp90 by GA resulted in an increase in superoxide generation and a decrease in eNOs protein expression. Decreased prostacyclin production was also found in ECs treated with GA. Conclusion: These in vitro HUVEC data suggest that increased endothelial oxidative stress may also occur in the fetal compartment during preeclampsia. 相似文献
16.
目的 :探讨热休克蛋白 70 (HSP70 )和Fas配体 (FasL)在子宫内膜异位症(EM)发病中的作用。方法 :采用免疫组化链霉菌抗生物素蛋白 -过氧化物酶染色法 (S P法 )检测子宫内膜异位症 5 6例的异位内膜与在位内膜 (30例 )中HSP70和FasL蛋白的表达 ,并以正常子宫内膜为对照 (2 5例 )。结果 :异位内膜组织中HSP70与FasL均呈高表达 ,与正常内膜组差异有高度显著性 (P <0 .0 1) ,而且二者失去在正常内膜组织中表达的周期性变化。但在卵巢子宫内膜异位症 (OEM)与子宫腺肌症 (AM)的表达差异无显著性 (P>0 .0 5 )。结论 :异位内膜组织中HSP70和FasL蛋白均过度表达 ,可能在EM的发病中起重要作用 相似文献
17.
Objectives To study the possibility of identifiable factors at or close to pregnancy that could predict hypertension later in life. To evaluate if women with hypertensive disease in their first pregnancy and who later develop hypertension also have characteristics of the metabolic syndrome. Methods Case control study of a cohort of women with hypertension diagnosed in first pregnancy ( n = 46) and controls without hypertension in pregnancy ( n = 47), studied 15 years after the index pregnancy. Blood pressure, antihypertensive drug treatment, body parameters, blood glucose, serum insulin, and serum lipids were analyzed. Results In the study group, 43% had hypertension compared to 4% in the control group. Among the women in the study group with more than one pregnancy, there was a significantly higher prevalence of hypertension if pregnancy-induced hypertension was repeated in a later pregnancy. There were also significantly higher waist/hip ratios and fasting plasma levels of insulin in the study group. Conclusion Hypertension in pregnancy is a strong predictor of hypertension later in life. Other factors related to hypertension and present at pregnancy are not useful in selecting a high-risk group. In a proportion of cases, the metabolic syndrome might be related to the hypertensive disease in pregnancy. 相似文献
19.
AbstractObjective: Heat shock protein 70 (Hsp70), a highly conserved cellular stress protein, is produced in every organism from bacteria to man. The purpose of this study was to determine the difference in Hsp70 concentrations between term and preterm deliveries. Methods: In total, 30 healthy term delivery and 99 preterm delivery (PD) women were recruited, including 46 women with preterm labor and intact membranes (PTL) with or without an intra-amniotic infection (IAI) and 53 women with a preterm premature rupture of membranes (PPROMs) with or without IAI. The Hsp70 levels in the maternal and the umbilical cord sera were tested by an enzyme-linked immunosorbent assay (ELISA); the expression levels of Hsp70 in the placentas were determined by immunoblotting and real-time PCR. Results: In contrast to the expression levels in normal term controls, Hsp70 expression levels were upregulated in PD; similar changes in Hsp70 expression levels were detected in PD maternal and umbilical sera. Patients with IAI were associated with a higher Hsp70 concentration than those without IAI. Conclusion: These results suggest a probable contributing role of altered Hsp70 expression levels in the pathophysiology of PD. 相似文献
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