血管内皮生长因子(VEGF)对培养内皮细胞VEGF受体表达的影响

目的 :为探讨VEGF对培养内皮细胞 (EC)VEGF受体表达的影响。方法 :将培养的人脐静脉内皮细胞 (HUVEC)随机分为 4组 :( 1)正常对照组 ;( 2 )低氧培养组 ;( 3)VEGF 10ng/ml组 ;( 4)低氧 +VEGF10ng/ml组。HUVEC低氧培养参照Kuwara等介绍的方法并加以改进。HUVECVEGF受体的检测采用免疫组织化学方法。结果 :采用简易低氧培养法 ,48h内培养液氧分压维持在 5 8mmHg ;与对照组相比 ,低氧培养组、VEGF组和低氧 +VEGF组HUVECVEGF受体Flk 1/KDR阳性细胞数增多 ,强度增加 ;但未检测到VEGF受体Flt 1表达。结论 :低氧可使HUVEC表面的VEGF受体Flk 1/KDR表达增加 ,VEGF同源上调其受体Flk 1/KDR ,低氧和VEGF在调节VEGF受体Flk 1/KDR方面有协调作用。     

Vascular Endothelial Growth Factor (VEGF) in Autoimmune Diseases

Vascular endothelial growth factor (VEGF) is a potent stimulating factor for angiogenesis and vascular permeability. There are eight isoforms with different and sometimes overlapping functions. The mechanisms of action are under investigation with emerging insights into overlapping pathways and cross-talk between other receptors such as the neuropilins, which were not previously associated to angiogenesis. VEGF has important physiological actions on embryonic development, healing, and menstrual cycle. It also has a great role in pathological conditions that are associated to autoimmune diseases. There is considerable evidence in various autoimmune diseases such as in systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis of an interrelationship between the VEGF system and theses disorders. Serum levels of VEGF correlate with disease activity in a large number of autoimmune diseases and fall with the use of standard therapy. We raised the possible future therapeutic strategies in autoimmune diseases with the anti-VEGF or anti-VEGFR (receptor). So far, this therapy has been used in cancer and macular ocular degeneration in diabetes. This review outlines the evidence for VEGF participation in various autoimmune diseases and proposes lines for future research in this field.     

Vascular Endothelial Growth Factor (VEGF) Expression in Human Pituitary Adenomas and Carcinomas

Vascular endothelial growth factor (VEGF) is a key mediator of endothelial cell proliferation, angiogenesis, and vascular permeability. Little is known about its expression in human pituitary adenomas. We examined 148 human pituitary adenomas for VEGF protein expression by immunohistochemistry. The strongest immunoreactivity was present in GH adenomas, corticotroph, silent corticotroph, silent subtype 3, and nononcocytic null cell adenomas. GH adenomas treated with octreotide strained less intensely than did untreated tumors. Relatively weak staining was present in PRL, gonadotroph, thyrotroph, and oncocytic null cell adenomas in the same sections showed evidence of down-regulation of VEGF protein expression in adenomas. Pituitary carcinomas usually had stronger staining than adenomas. In situ hybridization studies with oligonucleotide probes showed positive staining in all groups with stronger staining in GH, ACTH, TSH, and gonadotroph adenomas and in pituitary carcinomas. These results indicate that VEGF expression is more prominent in certain adenoma subtypes, that decreased expression occurs in adenomas as compared to nontumorous pituitary and that carcinomas show increased VEGF expression relative to adenomas suggesting up-regulation of VEGF during pituitary tumor progression.     

Immunohistochemical Expression of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor in Canine Cutaneous Fibrosarcomas

The expression of five markers associated with tumour angiogenesis, proliferation and apoptosis was studied in 24 canine cutaneous fibrosarcomas. Tumours were assigned histological grades and were immunohistochemically evaluated for the expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2). Additionally, intra-tumour microvessel density (iMVD) was assessed by immunohistochemical labelling for expression of von Willebrand factor (vWf) and tumour proliferation index (PI) was measured following labelling of Ki-67 antigen. Finally, tumour apoptotic index (AI) was determined by application of the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP end-labelling method (TUNEL). VEGF and VEGFR-2 expression were detected in 22/24 (92%) and 24/24 (100%) of fibrosarcomas, respectively. There was correlation between VEGF and VEGFR-2 expression (r = 0.51) and between histological grade and PI (r = 0.82). A significant difference in PI between tumours of different histological grade was found (P < 0.05). The median PI in grade 2 and 3 tumours (30.6 and 54.7, respectively) was significantly higher than in grade 1 tumours (6.4). Therefore, only PI correlates significantly with the histological grade of canine cutaneous fibrosarcomas. The potential for autocrine activity for VEGF exists in canine cutaneous fibrosarcomas, as VEGF and VEGFR-2 expression was found in most tumours.     

长期大强度游泳对大脑血管内皮细胞生长因子(VEGF)的影响

研究长时间大强度游泳训练对大鼠大脑皮质VEGF表达的影响,探讨大脑皮质微循环变化与VEGF表达的变化之间的关系,可为深入研究大脑微循环与运动性中枢疲劳的发生机制提供基础实验资料.采用VEGF免疫组化染色和Ⅶ因子免疫荧光染色用Nikon&Spot计算机图像自动分析系统进行分析.结果显示(1)长时间大强度游泳训练可以加强大鼠大脑皮质特异部位的VEGF表达;(2)内皮细胞VEGF阳性表达和神经元的阳性表达以及微血管面积三者之间存在同步关系;(3)VEGF在大脑皮质微血管的作用可能以改变内皮细胞通透性功能为主,而在神经元表达的VEGF可能具有某种神经内分泌功能,参与了改变大脑皮质局部微循环的过程.     

The Role of Vascular Endothelial Growth Factor (VEGF) in Abnormal Vascular Changes in the Adult Rat Eye

Abstract

The aim of this project was to determine if the subretinal delivery of a recombinant adenovirus encoding vascular endothelial growth factor (VEGF) was sufficient to induce changes resembling choroidal neovascularisation (CNV) in a rat model. A recombinant adenovirus was produced encoding vegf¹⁶⁴ cDNA (Ad.RSV.VEGF). Transduction of cultured RPE cells confirmed VEGF expression and ensured the absence of Ad.RSV.VEGF-related toxicity. Following subretinal injection into rat eyes, fluorescein angiography indicated that the in vivo delivery of Ad.RSV.VEGF was associated with vascular leakage. Histological analysis demonstrated that changes resembling the early signs of CNV development were also present in the Ad.RSV.VEGF injected eyes. These results suggest that while a transient VEGF expression in the RPE layer is able to induce CNV-related changes, it may be insufficient for the development of a full neovascular membrane. This study demonstrates that virus-mediated gene delivery, in addition to its clinical applications, is a potentially efficient research tool for investigating gene expression-related physiological changes in vitro and in vivo.     

人胎儿股骨发生过程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)与人胚胎骨发生及发育的关系。方法用免疫组化技术对11~36 W人胎儿股骨中血管内皮生长因子的分布和表达情况进行了研究。结果VEGF阳性反应主要见于成骨细胞、破骨细胞及新生骨细胞中,血管内皮细胞及骨髓细胞也呈阳性反应;骺软骨钙化区肥大的软骨细胞为VEGF阳性反应,但其它区域的软骨细胞中无VEGF表达。结论VEGF在胚胎发生时期在血管内皮细胞和成骨细胞的表达,说明VEGF在人胎儿骨发生及发育过程中发挥重要作用。     

Integrated Effects of Matrix Mechanics and Vascular Endothelial Growth Factor (VEGF) on Capillary Sprouting

Angiogenesis is the growth of new capillaries from existing vasculature. Vascular network formation is known to be regulated by the biophysical and biochemical signals emanating from the microenvironment. However, it is not clear how endothelial cells integrate these signals to drive the capillary morphogenesis. In this study, human umbilical endothelial cells (HUVECs) were seeded on scaffolds with varying stiffness and capillary formation was quantified. Our study revealed that cells formed well defined networks on compliant gels. Increase in stiffness resulted in a decrease in sprouting. VEGF was encapsulated within the scaffolds at concentrations ranging from 0 to 100 ng/mL to investigate the interplay between VEGF concentration profiles and matrix stiffness in guiding network formation. Quantitative analysis revealed that while VEGF disrupted sprout formation on compliant substrates, it elicited a sprouting response in cells seeded on scaffolds of intermediate rigidity. Additionally, we also observed that a minimum cell density is required for the formation of well-connected vascular networks.     

PPAR-γ激动剂对2型糖尿病大鼠肾脏血管内皮生长因子表达的影响

目的探讨PPAR-γ激动剂罗格列酮对糖尿病大鼠肾脏VEGF表达的影响。方法采用长期高脂饮食加小剂量链脲菌素（STZ）一次性腹腔注射，建立2型糖尿病大鼠模型，光镜及电镜行肾脏形态学检查；RT—PCR测定VEGF mRNA表达，VEGF免疫组化染色观察VEGF蛋白水平变化。结果2型糖尿病大鼠肾脏VEGFmRNA及其蛋白质表达明显高于正常对照组（均P〈0．01），同时大鼠肾脏出现糖尿病肾病的病理变化；PPAR-γ激动剂罗格列酮干预后，肾组织VEGF mRNA及其蛋白质表达较2型糖尿病组降低（均P〈0．01）,同时肾脏病理变化也得到明显改善。结论PPAR-γ激动剂罗格列酮可能通过抑制肾脏VEGF表达，延缓糖尿病肾病的发生。     

脂质体介导的VEGF_(165)基因转染对内皮细胞生长的作用

构建血管内皮细胞生长因子基因VEGF165真核表达载体pcDNA3 VEGF165,以阳离子脂质体介导的基因转染技术 ,将基因转入原代培养的人脐静脉内皮细胞中。结果表明 ,基因转染 1h后细胞内就有VEGFDNA存在 ,VEGFmRNA水平显著上升 ;基因转染 2d后培养液上清VEGF蛋白表达显著上升 (135 5 12± 6 2 34)pg/ml和 (19 2 7± 2 96 )pg/ml,P <0 0 1。转染VEGF165基因 2d的内皮细胞再经程序降温冷冻保存复苏后 ,其存活率显著高于对照组 (pcDNA3 组 ) (90 13%± 2 84 %和81 5 2 %± 2 15 % ,P <0 0 5 ) ,凋亡率显著低于对照组 (7 15 %± 0 4 2 %和 17 6 1%± 1 5 6 % ,P <0 0 5 )。MTT法显示转染VEGF165基因能促进内皮细胞VEGF蛋白的表达 ,促进细胞增殖 ,抑制细胞凋亡。在治疗心脏及下肢动脉缺血性疾病中 ,VEGF165基因治疗可能具有重要的意义。     

Role of Vascular Endothelial Growth Factor (VEGF) in the Neurological Manifestations of Dengue: A Preliminary Study

This study reports on vascular endothelial growth factor (VEGF) in dengue patients with neurological manifestations. Their bleeding diathesis, hypotension, edema, flushing, and hepatosplenomegaly were noted. Complete blood counts, serum chemistry, coagulation profile, liver and kidney function tests, creatine kinase (CK), and MRI in encephalopathic patients were carried out. Serum VEGF was estimated by ELISA in 21 dengue patients and 14 controls. Twelve patients had dengue fever (DF), eight dengue hemorrhagic fever (DHF), and one dengue shock syndrome (DSS). Fifteen patients had neurological manifestation, 12 had muscle involvement (raised CK with or without weakness), and 3 had encephalopathy. The VEGF level in dengue patients was 50.0?±?56.1 pg/mL and in the controls, 60.6?±?20.3 pg/mL. The VEGF level neither correlated with the severity nor with the neurological involvement. Thrombocytopenia, however, correlated with the severity of dengue and neurological manifestations. The VEGF level is not related to the severity of dengue and neurological syndrome.     

乳腺癌患者血清Leptin和VEGF的表达

目的：研究瘦素（Leptin）、血管内皮生长因子（VEGF）在乳腺癌患者血清中的表达，探讨其在乳腺癌诊断中的意义。方法：选择乳腺癌患者36例，乳腺良性增生病变患者31例，另选56例健康女性作为对照。分别用放射免疫分析（RIA）和酶联免疫吸附试验（ELISA）测定这些患者术前血清Leptin、VEGF。结果：正常对照组与良性病变组、乳腺癌组Leptin存在明显差异，正常对照组与乳腺癌组，良性病变组与乳腺癌组VEGF存在明显差异。乳腺癌患者术前血清Leptin、VEGF含量与有无淋巴结转移具有相关性。结论：乳腺癌患者术前血清Leptin、VEGF可作为鉴别乳腺良恶性肿瘤有无转移的指标。     

Expression of Vascular Endothelial Growth Factor Isoforms in the Japanese Quail Embryo

Vascular endothelial growth factor (VEGF) is required for vascular development. In the quail, four VEGF isoforms formed by alternative splicing, are translated into proteins with 122, 146, 166, and 190 amino acids. VEGF isoforms differ biochemically, with variable affinities for heparan sulfate proteoglycans, the extracellular matrix and VEGF receptors. There are few data on the functional significance of VEGF isoforms. RT-PCR was used to examine isoform expression during quail vascular development. Our results suggest that all quail isoforms are expressed during establishment of the vascular pattern in whole embryos and extraembryonic tissues at apparently equal levels. No isoform-specific expression patterns were detected in isolated endoderm or between embryo halves.     

Immunohistochemical Expression of Vascular Endothelial Growth Factor in Canine Mammary Tumours

The histopathological and clinical aspects of canine mammary tumours (CMTs) have been widely studied, but the variation in the biological behaviour of these neoplasms hampers the identification of prognostic factors. Sustained angiogenesis has been suggested to be one of the most important factors underlying tumour growth and invasion. This process involves the action of several growth factors including vascular endothelial growth factor (VEGF). The present study characterizes the relationship between immunohistochemical expression of VEGF and gross (e.g. size and tissue fixation) and microscopical (e.g. type, growth, necrosis, lymphoid infiltration, lymph node metastasis, histological grade and proliferation index) features of CMTs. Forty-eight benign and 64 malignant CMTs were evaluated. Statistical analysis failed to show a significant relationship between VEGF expression and the pathological features, suggesting that VEGF expression occurs in both benign and malignant tumours and is independent of histological type, proliferation, tissue invasion or local metastatic capacity.     

Airway Administration of Vascular Endothelial Growth Factor siRNAs Induces Transient Airspace Enlargement in Mice

Purpose: Reduction in the level of vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of pulmonary emphysema. To this end, pharmacological VEGF receptor blockade, and the Cre-lox system models have been utilized to study the effects of VEGF depletion in the lung. These models generally reproduce air space enlargement resembling clinical emphysema. Here we report a potentially more readily available model of lung targeted VEGF depletion by airway administration of VEGF small inhibitory RNA oligonucleotides (siRNAs) in mice.Methods: Airway administration of VEGF siRNAs were done in C57BL/6 mice. The lungs were removed for histology and protein analysis 2, and 4 days later. Airspace enlargement was evaluated by lung volume measurement, and histological analyses. VEGF levels were analyzed by western blot and immunohistochemistry.Results: Airway administration of VEGF siRNAs induced transient air space enlargement in the mouse lung morphologically resembling the previously reported models of pulmonary emphysema. VEGF expression was significantly reduced in the lung, particularly in the alveolar septal cells. We also found that in this particular model, sequential airway administration of recombinant VEGF protein attenuated this air space enlargement. Additionally, we found that airway administration of DCI, a combination of dexamethasone, 3''-5''-cyclic adenosine monophosphate, and isobutylmethylxanthine attenuated the air space enlargement in this particular model, at least in part through the recovery of lung VEGF expression.Conclusions: The pathogenesis of pulmonary emphysema is likely to be multifaceted, but the present mouse model may be useful in dissecting the involvement of VEGF in pulmonary emphysema.     

血管内皮生长因子分子多样性及其与肿瘤的关系

血管内皮生长因子是肿瘤发生发展过程中起重要作用的一类糖蛋白,其在基因水平存在较多的SNP位点以及在RNA剪切水平上存在选择性剪切.研究表明,这些变异与各种肿瘤的发生、发展、恶性程度有着密切的关系.     

Angiogenesis and the Expression of Vascular Endothelial Growth Factor in Endometrium and Placenta

PROBLEM: The demand for increased angiogenesis and microvascular permeability during cyclical changes in the endometrium and during placentation raises the possibility that aberrations in these events could lead to suboptimal reproductive performance. However, relatively little is presently known regarding the regulation of vascular growth and permeability in these tissues. METHOD OF STUDY: This review of current literature focuses on the expression, regulation, and potential physiological effects of vascular endothelial growth factor (VEGF) within endometrial and placental tissue. RESULTS: Spatial and temporal expression of VEGF as well as its restricted specificity, essential role in vasculogenesis/angiogenesis, and ability to induce vascular permeability makes VEGF an attractive regulator of vascular growth and permeability in the endometrium and placenta. CONCLUSION: A better understanding of the production, regulation, and physiological responses of the vasculature to angiogenic growth factors may lead to new therapeutic strategies for reproductive disturbances secondary to vascular insufficiencies within the female reproductive tract.     

2型糖尿病肾病患者血管内皮生长因子检测的临床意义

目的 :探讨了 2型糖尿病肾病患者血管内皮生长因子的水平。方法 :应用酶联双抗体夹心法测定了 31例无糖尿病肾病和 5 5例糖尿病肾病患者血管内皮生长因子含量 ,并与 35名正常健康人作对照。结果 :2型糖尿病无肾病组和有肾病组血管内皮生长因子水平均高于正常人组 ,尤以糖尿病肾病为甚 (p <0 0 1 ) ,糖尿病肾病组与无糖尿病肾病组比较 ,差异也有显著性 (p <0 0 1 )。 结论 :2型糖尿病肾病的发生与发展与血管内皮生长因子水平密切相关。