妊娠高血压综合征患者胎盘组织中血管内皮生长因子的表达

目的　探讨血管内皮生长因子（VEGF）在妊娠高血压综合征（妊高征）患者胎盘组织中的表达及对妊高征患者胎盘滋养细胞功能和绒毛毛细血管网形成的影响。方法　采用免疫组织化学SP法检测21例正常孕妇（对照组）,60例妊高征患者（妊高征组,其中轻、中、重度妊高征患者各20例）胎盘组织VEGF的表达强度。结果　VEGF主要表达于胎盘绒毛滋养细胞;中度及重度妊高征患者胎盘绒毛滋养细胞VEGF表达强度均明显低于对照组及轻度妊高征患者(P＜0.05),而轻度妊高征患者与对照组比较,差异无显著性(P＞0.05),各组间蜕膜组织VEGF表达强度差异无显著性(P＞0.05)。　结论　VEGF在胎盘中主要由绒毛滋养细胞分泌,妊高征患者VEGF分泌减少,可能是引起局部胎盘绒毛及血管病变的原因之一。     

胎盘生长因子与妊高征发病的关系

胎盘生长因子(PlGF),属于血管内皮生长因子(VEGF)家族成员,可以诱导内皮细胞增殖、移行,能增强VEGF的生物活性,促进滋养细胞增殖.主要合成部位是滋养细胞,缺氧下调PlGF的表达,妊高征病人血清PlGF水平下降.PlGF的受体Flt-1(fms-like tyrosine kinase-1)位于血管内皮细胞和滋养细胞,推测妊高征胎盘PlGF产生异常有可能是构成这种疾病血管损伤、滋养细胞功能异常的一个因素.     

胎盘血管生长因子在妊娠高血压综合征的表达及意义

目的　通过比较正常孕妇与妊娠高血压综合征(妊高征)患者胎盘分泌的血管生长因子,包括血管内皮生长因子、碱性成纤维细胞生长因子及血小板来源生长因子的表达变化,探讨血管生长因子在妊高征的表达及意义。　方法　采集正常孕妇(15例)及妊高征患者(19例)的胎盘组织,采用免疫组织化学PAP法结合计算机显微图像分析软件,检测胎盘血管生长因子的表达。　结果　妊高征组中,中、重度妊高征患者胎盘的血管内皮生长因子阳性反应平均灰度值为 61.6±3.7,明显低于正常妊娠组的71.1±5.8和轻度妊高征的70.9±8.9,差异有统计学意义(P<0.01);碱性成纤维细胞生长因子阳性反应平均灰度值为 60.9±8.8,较正常妊娠组的 79.7±7.6 和轻度妊高征的78.4±10.4明显下降,差异有统计学意义(P<0.01);血小板来源生长因子阳性反应平均灰度值为37.5±5.6,较正常妊娠组的22.1±3.1和轻度妊高征的 21.8±4.3 明显增加,差异亦有统计学意义(P<0.01)。　结论　胎盘血管生长因子表达异常,可能导致胎盘血管面积下降,胎盘血管壁张力增高、痉挛,从而影响胎盘的血液供应,导致妊高征的一系列病理生理改变;表达异常的程度与妊高征病情轻重有关。     

胎盘生长因子与妊高征发病的关系

胎盘生长因子（P1GF），属于血管内皮生长因子（VEGF）家族成员，可以诱导内皮细胞增殖、移行，能增强VEGF的生物活性，促进滋养细胞增殖。主要合成部位是滋养细胞，缺氧下调P1GF的表达。妊高征病人血清P1GF水平下降，P1GF的受体Flt-1(fms-like tyrosine kinase-1)位于血管内皮细胞和滋养细胞，推测妊高征胎盘P1GF产生异常有可能是构成这种疾病血管损伤，滋养细胞功能异常的一个因素。     

血管内皮生长因子与妊娠高血压综合征发病的相关性研究

目的探讨血管内皮生长因子（VEGF）与妊娠高血压综合征（妊高征）发病的相关性。方法采用酶联免疫吸附法检测23例妊高征患者（妊高征组）外周血及其新生儿脐静脉血VEGF水平,定量免疫组化及定量逆转录聚合酶链反应检测患者胎盘和蜕膜组织中VEGF表达情况,并以20例健康孕妇(正常妊娠组)为对照。结果（1）妊高征组外周血VEGF水平为［(10.4±3.8)ng/L,±s,下同］,明显低于正常妊娠组的(17.0±9.3)ng/L。（2）胎盘合体滋养细胞及蜕膜间质滋养细胞均有VEGF强阳性染色。经计算机扫描图像处理,正常妊娠组绒毛合体滋养细胞VEGF表达为(75.0±9.0)平均灰度,间质细胞为(60.5±6.4)平均灰度,均显著高于妊高征组的(69.0±8.9)平均灰度和(55.0±7.3)平均灰度。正常妊娠组VEGF表达为(45.4±4.0)平均灰度,显著高于妊高征组的(42.5±3.8)平均灰度。（3）胎盘、蜕膜组织均有3种不同片断长度的VEGFmRNA扩增,正常妊娠组胎盘组织VEGF总峰度比为2.8±1.0,较妊高征组(4.6±3.2)极明显降低（P<0.01）。正常妊娠组蜕膜组织VEGF总峰度比为3.9±1.5,也较妊高征组(6.3±2.9)极明显降低,（P<0.01）。结论妊高征患者VEGF表达障碍发生在蛋白质翻译和表达水平;VEGF的异常表达在妊高征胎盘缺氧中具有重要的作用。     

血管内皮生长因子及受体对妊娠高血压综合征发病的影响

目的:探讨血管内皮生长因子(VEGF)及受体(FLT-1)在妊娠高血压综合征(妊高征)发病中的作用。方法:选取妊高征孕妇51例,正常妊娠妇女44例(其中晚期妊娠23例),及非妊娠妇女10例为研究对象。采用ELISA方法测定其血清VEGF水平;以免疫组织化学方法观察VEGF及受体FLT-1在胎盘绒毛中的表达。结果:妊高征组血清VEGF水平为23.39±9.79ng/L,明显低于正常晚期妊娠组(40.62±14.85ng/L),(P<0.01)。胎盘中VEGF及肿-1的表达较正常晚期妊娠组弱,有显著性差异(P<0.05)。轻度妊高征组血清VEGF水平为33.79±5.97ng/L,与正常晚期妊娠组比较无明显差异(P>0.05)。中、重度妊高征组VEGF水平分别为21.44±2.07ng/L、16.45±5.56ng/L,与晚期妊娠组比较,差异有显著性(P<0.01)。结论:孕妇血清中VEGF水平下降、胎盘中VEGF及FLT-1表达降低可能与妊高征的发病机理有关。     

VEGF及其在妊娠中的作用

VEGF具有促进血管通透性增加、血管内皮细胞分裂、增殖及诱导血管生成等作用.在人类胎盘滋养细胞及血管内皮细胞上有VEGR及其受体的表达,说明VEGF参与正常妊娠、胎盘血管生成的调节和滋养叶细胞生理性的侵入.妊高征患者外周血VEGF及妊高征胎盘中VEGF mRNA水平明显降低可造成滋养细胞侵入缺陷,而使母体子宫血管转变不足,造成胎盘灌注不足.     

VEGF及其在妊娠中的作用

VEGF具有促进血管通透性增加,血管内皮细胞分裂、增殖及诱导血管生成等作用。在人类胎盘滋养细胞及血管内皮细胞上有VEGR及其受体的表达。说明VEGF参与正常妊娠,胎盘血管生成的调节和滋养叶细胞生理性的侵入,妊高征患者外周血VEGF及妊高征胎盘中VEGFmRNA水平明显降低可造成滋养细胞侵入缺陷,而使母体子宫血管转变不足,造成胎盘灌注不足。     

血管内皮生长因子与妊娠高血压综合征发病及一氧化氮的关系

目的　探讨血管内皮生长因子（VEGF）在妊娠高血压综合征（妊高征）发病中的作用,及其与一氧化氮（NO）的关系。方法　选择妊高征患者(妊高征组)41例,其中轻度妊高征12例,中度妊高征13例,重度妊高征16例;选择同期正常晚期妊娠妇女20例为对照组。采用酶联免疫吸附法测定两组孕妇血清VEGF水平,用硝酸盐还原酶法测定两组胎盘组织NO浓度变化。结果　（1）妊高征组血清VEGF水平明显低于对照组,轻度妊高征患者血清VEGF水平与对照组比较,差异无显著性,中、重度妊高征患者血清VEGF水平分别为（23.1±4.1）ng/L、（14.8±3.9）ng/L,明显低于对照组。（2）妊高征组胎盘组织中NO浓度较对照组明显降低,轻度妊高征患者胎盘组织NO浓度与对照组比较,差异无显著性,中、重度妊高征患者胎盘组织NO浓度分别为（9.1±2.1）μmol/g、(5.6±1.8)μmol/g,均明显低于对照组。（3）血清VEGF水平与胎盘组织NO浓度呈显著正相关（r=0.65,P<0.01）。结论　妊高征患者血清中VEGF水平降低,胎盘组织中NO浓度下降,可能在妊高征的发病中起一定作用。     

正常妊娠和妊高征胎盘中血管内皮生长因子的表达及其意义

目的　观察血管内皮生长因子（ＶＥＧＦ）在妊高征（ＰＩＨ） 胎盘中的变化。　方法　用免疫组织化学法,检测２０ 例正常妊娠胎盘（ 对照组）和２３ 例妊高征胎盘（ 妊高征组） 中ＶＥＧＦ的水平。　结果ＶＥＧＦ在正常妊娠胎盘和妊高征胎盘中分布基本一致,分布在滋养细胞、血管及绒毛间质。在妊高征组ＶＥＧＦ为轻度表达占７９－２％ ,无重度表达;而在对照组ＶＥＧＦ 轻度表达占２５％ ,中度表达占４５％ ,重度表达占３０ ％ 。妊高征组中ＶＥＧＦ表达明显低于对照组（ Ｐ＜ ０．０１）。　结论　妊高征胎盘中ＶＥＧＦ的减少可能与胎盘血管生成减少及胎盘滋养叶细胞侵入异常有关,在妊高征发病中占有一定的地位。     

胎盘生长因子在高危妊娠中的研究进展

妊娠是复杂的生理过程,胎盘通过营养、代谢、交换、内分泌等作用调节母儿循环,是母儿联系的桥梁,对胎儿的生长发育及母体生理机能改变起着重要的作用。胎盘的正常发育及良好的生理功能是维持妊娠及胎儿生长发育的先决条件。胎盘形成及功能异常与妊娠期高血压疾病(hypertensive disorders of pregnancy,HDP)、胎儿生长受限(fetal growth restriction,FGR)、流产和唐氏综合征(Down′s syndrome,DS)等的发生密切相关。胎盘生长因子(placenta growth factor,PlGF)是丰富表达于胎盘的一种重要的生长因子,与血管内皮生长因子(vascular endothelial growth factors,VEGF)具有高度同源性,主要由滋养细胞和绒毛间质内皮细胞分泌,对滋养细胞增殖、活化及胎儿胎盘血管网形成起重要作用,故对PlGF进行深入研究对胎盘形成异常相关疾病的病因学研究及临床监测均具有重要意义。     

Co-localization of vascular endothelial growth factor and its two receptors flt-1 and kdr in the mink placenta

Placental angiogenesis plays an important role in placental development and morphogenesis. Vascular endothelial growth factor (VEGF) is a well-known angiogenic growth factor, which has previously been localized in different epitheliochorial and haemochorial placenta types. In the present study VEGF and its Flt-1(VEGFR-1) and KDR (VEGFR-2) receptors were immunolocalized in the endotheliochorial mink placenta throughout gestation. VEGF, Flt-1 and KDR co-localized to fetal and maternal microvascular endothelial cells, but with a temporal difference, displaying KDR in endothelial cells throughout gestation, whereas the VEGF and Flt-1 maternal endothelial cell staining was most intense during late gestation. Additionally, KDR was found in vascular related mesenchymal cells. The VEGF-receptors were also localized in non-endothelial cells, e.g. the uterine luminal and glandular epithelium as well as the trophoblast. Our results are in agreement with former studies, showing the different effects of the Flt-1-and KDR receptors in respect of angiogenesis. More importantly, the present study of the endotheliochorial placenta localizes the VEGF-ligand-receptor system in non-endothelial cells, and thereby strengthen the hypothesis that VEGF, apart from its well-established angiogenic properties, must also have additional functional roles in the establishment and development of the placenta.     

Placental vascular morphogenesis

Appropriate growth and development of the placenta is essential for fetal growth and wellbeing, and indeed may be an important factor in determining adult health. As the fetus grows its demands increase and the capacity of the placenta to facilitate transfer between the fetal and maternal circulations increases as gestation progresses. The principal units for diffusional exchange of oxygen are the terminal villi, and these develop in the third trimester. It is thought that capillary growth within the villi drives the growth of these structures which are characterized by a high proportion of their volume being occupied by fetal capillaries and extreme thinning of the trophoblast and endothelial cell layers. In the first trimester the PO2 in the intervillous space is low and rises sharply at the start of the second. Endothelial growth is influenced by a variety of soluble factors, and several of these are regulated by oxygen, for example, vascular endothelial growth factor (VEGF), angiopoietin 2, and soluble flt (a VEGF antagonist). Thus, fetal demand may regulate villous growth and differentiation by altering local PO2 which, in turn, modulates growth factors (or their antagonists) to regulate endothelial growth and vessel re-modelling.     

Lymphokine-activated killer cells induced from decidual lymphocytes reduce the angiogenic activity of trophoblasts by enhancing the release of soluble fms-like tyrosine kinase-1 from trophoblasts: an implication for the pathophysiology of preeclampsia

T helper (Th)1 cytokine-predominating status and compromised placental vasculature is thought to be central to the pathogenesis of preeclampsia. However, it remains to be clarified how these two phenomena relate to each other. We have reported that lymphokine-activated killer (LAK) cells induced from decidual mononuclear cells (DMCs) with interleukin (IL)-2 expressed in preeclamptic placenta reduced the angiogenic activity of cytotrophoblasts (CTs). The objective of this study was to examine how LAK cells reduced the angiogenic activity of CTs. We investigated the angiogenesis-related molecules released from cultured CTs obtained from first trimester placenta that had been pretreated with either non-activated DMCs or LAK cells from DMCs. The amounts of vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and their antagonist, soluble fms-like tyrosine-kinase-1 (sFlt-1) released in CT culture media were measured using ELISA. CTs pretreated with LAK cells released more sFlt-1 compared with those pretreated with non-activated lymphocytes, and CTs pretreated with non-activated lymphocytes released more sFlt-1 compared with those without pretreatment. The release of total VEGF and free PlGF from CTs was not altered by pretreatment with DMCs. Thus, in preeclamptic placenta, LAK cells induced from DMCs by co-existing IL-2 may react to the invading CTs and enhance the release of sFlt-1 from CTs without any change of VEGF or PlGF secretion. This might result in the reduction of actual angiogenic potential of the VEGF system in decidua and the placental vascular system might be compromised, which may lead to the development of preeclampsia.     

Placental expression of EG-VEGF and its receptors PKR1 (prokineticin receptor-1) and PKR2 throughout mouse gestation

Compelling evidence indicates that vascular endothelial growth factor (VEGF) is an important mediator of placental angiogenesis and appears to be disregulated in pre-eclampsia (PE). Recently, we characterised the expression of EG-VEGF (endocrine gland-derived vascular endothelial growth factor), also known as prokineticin 1 (PK1) in human placenta during the first trimester of pregnancy and showed that this factor is likely to play an important role in human placentation. However, because it is impossible to prospectively study placentation in humans, it has been impossible to further characterise EG-VEGF expression throughout complete gestation and especially at critical gestational ages for PE development. In the present study, we used mouse placenta to further characterise EG-VEGF expression throughout gestation. We investigated the pattern of expression of EG-VEGF and its receptors, PKR1 and PKR2 at the mRNA and protein levels. Our results show that EG-VEGF and VEGF exhibit different patterns of expression and different localisations in the mouse placenta. EG-VEGF was mainly localised in the labyrinth whereas VEGF was mainly present in glycogen and giant cells. EG-VEGF mRNA and protein levels were highest before 10.5days post coitus (dpc) whereas those of VEGF showed stable expression throughout gestation. PKR1 protein was localised to the labyrinth layer and showed the same pattern of expression as EG-VEGF whereas PKR2 expression was maintained over 10.5dpc with both trophoblastic and endothelial cell localisations. Altogether these findings suggest that EG-VEGF may have a direct effect on both endothelial and trophoblastic cells and is likely to play an important role in mouse placentation.     

The characterization of fibrocyte-like cells: a novel fibroblastic cell of the placenta

The placenta is a highly vascularized organ thus angiogenesis is a key process in placental development. The contribution that different cells in the villous stroma play in placental angiogenesis is largely unknown. In this study we identified a novel stromal cell type in sections of term placenta which is morphologically fibroblastic and expressing the fibroblast marker TE-7 but also positive for the monocytic markers CD115 and CD14 and designated these cells as fibrocyte-like cells. Populations of fibrocyte-like cells from the placenta were isolated by two methods: culture of adherence-selected placental cells and, for higher purity, by CD45 fluorescence activated cell sorting (FACS). Fibrocyte-like cell conditioned medium increased endothelial tubule-like structure formation 2-fold versus control medium. Both pro-angiogenic growth factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) and the anti-angiogenic factor soluble-Flt were found in the conditioned medium. Neutralizing antibodies against VEGF and b-FGF reduced endothelial cell tubule-like structures to control levels. These data suggests that fibrocyte-like cells, a previously unidentified cell of the villous stroma, may play an important role in the regulation of placental angiogenesis.