血管内皮细胞生长因子在肥胖乳腺癌患者乳腺癌组织中的表达及临床意义

 摘要：　目的 探讨肥胖乳腺癌患者乳腺癌组织中血管内皮细胞生长因子（vascular endothelial growth factor,VEGF）的表达及临床意义。方法 采集45例肥胖乳腺癌患者,37例正常体重乳腺癌患者,用RT-PCR和免疫组织化学检测肥胖组和正常体重组乳腺癌组织VEGF的mRNA和蛋白表达。结果 肥胖组乳腺癌组织VEGF的mRNA和蛋白表达均高于正常体重组 (P<0.05),并且VEGF mRNA和蛋白表达之间呈正相关(r=0.785,P<0.05);VEGF在肥胖乳腺癌组织中的表达与组织学分级、5年复发转移有关,与患者年龄无关。结论 VEGF在肥胖乳腺癌患者中具有高表达趋势,提示VEGF可能在肥胖相关性乳腺癌的发生、演变及预后中起重要作用。     

Peritumoral brain edema in angiomatous supratentorial meningiomas: an investigation of the vascular endothelial growth factor A pathway

The aim of this work was to study the vascular endothelial growth factor A (VEGF‐A) pathway and peritumoral brain edema (PTBE) through comparison of non‐angiomatous and angiomatous meningiomas. Meningiomas are common intracranial tumors, which often have PTBE. VEGF‐A is an integral part of PTBE formation and angiogenesis, and the capillary‐rich angiomatous meningiomas are known for their PTBE. The VEGF‐A receptor VEGFR‐2 is responsible for the angiogenic effect of VEGF‐A on endothelial cells, which is enhanced by the co‐receptor neuropilin‐1. Forty non‐angiomatous, 22 angiomatous meningiomas, and 10 control tissue samples were collected for the study. Magnetic resonance images were available for 40 non‐angiomatous and 10 angiomatous meningiomas. Tissue sections were immunostained for CD34, MIB‐1, estrogen‐ and progesterone receptors. ELISA, chemiluminescence, and RT‐qPCR were used for VEGF‐A, VEGFR‐2, and neuropilin‐1 protein and mRNA quantification. Angiomatous meningiomas had larger PTBE (695 vs 218 cm³, p = 0.0045) and longer capillary length (3614 vs 605 mm/mm³, p < 0.0001). VEGF‐A mRNA, neuropilin‐1 mRNA, and VEGFR‐2 protein levels were higher in angiomatous meningiomas independently of the capillary length (p < 0.05). Neuropilin‐1 protein levels were lower in angiomatous meningiomas (p < 0.0001). The VEGF‐A pathway and tumor capillary length may be essential for PTBE‐formation in meningiomas. Further investigations of this pathway could lead to earlier therapy and targeted pharmacological treatment options.     

Association of vascular endothelial growth factor gene polymorphisms with recurrent spontaneous abortion in Chinese Han women

Citation Xing X, Yan J, Zhao Y, You L, Bian Y, Chen Z‐J. Association of vascular endothelial growth factor gene polymorphisms with recurrent spontaneous abortion in Chinese Han women. Am J Reprod Immunol 2011; 65: 521–525 Problem An association of polymorphism ?1154G/A (rs1570360) in vascular endothelial growth factor (VEGF) gene with idiopathic recurrent spontaneous abortion (RSA) has been found in Caucasians. The aim of this study was to examine the association of VEGF ?1154 with RSA in a well‐defined group of Chinese Han patients. Method of study The VEGF ?1154G/A genotype was detected by real‐time PCR with TaqMan probes. The products were also subjected to gene sequence analysis to validate the PCR results. Results The allele frequencies of VEGF ?1154G/A showed no significant difference between RSA patients and the normal controls (P = 0.183). The frequencies of VEGF ?1154G/A genotypes were not significantly different between RSA patients and the normal controls (P = 0.228). Conclusion Our study revealed that VEGF ?1154G/A polymorphism was not associated with the susceptibility to RSA in Chinese Han women.     

Nicotine potentiates vascular endothelial growth factor expression in balloon-injured rabbit aortas

Both nicotine and vascular endothelial growth factor (VEGF) have been proposed to play an important role in the development and progression of atherosclerosis. In vitro and ex vivo studies have demonstrated that nicotine significantly stimulates VEGF expression in several cell types. This study examined the effects and the mechanisms of nicotine on the expression of VEGF in a rabbit model of balloon-injured aortas. Forty-eight male New Zealand white rabbits were randomly divided into sham, control, nicotine, and nicotine plus hexamethonium (nicotine–hex) groups. Balloon catheter denuding injury iliac artery was performed in control, nicotine, and nicotine–hex animals fed with a high-cholesterol diet beginning 2 weeks before operation. Twenty-four hours after surgery, nicotine (0.05 μg/kg) or nicotine (0.05 μg/kg) and hexamethonium (6 mg/kg) was administered daily by intramuscular injection for 3 weeks in nicotine and nicotine–hex groups, respectively. Sham and control rabbits received an identical volume of phosphate-buffered saline injection, but without nicotine or hexamethonium. VEGF protein expression and intimal cell proliferation in balloon-injured aortas were determined by enzyme-link immunosorbent assay, immunohistochemistry, and Western blot analysis. Six rabbits died during the experiment. The remaining 42 rabbits were included in the study. VEGF protein expression in nicotine group was significantly higher than that in control group (P < 0.01). VEGF positive staining was seen in vascular endothelial cells, vascular smooth muscle cells, and infiltrative inflammatory cells. The number of the proliferative cells in intima was also significantly higher in nicotine group than in control group (P < 0.01). Hexamethonium, a nonselective antagonist of nicotinic acetylcholine receptors (nAChRs), significantly inhibited nicotine-induced VEGF protein expression (P < 0.01). The present study shows that intramuscular administration of nicotine markedly potentiates the expression of VEGF protein in balloon-injured rabbit aortas, which appears to be mediated through nAChRs.     

Circulating vascular endothelial growth factor concentrations in patients with postmenopausal osteoporosis

Introduction

The role of vascular endothelial growth factor (VEGF) in osteoporosis has not yet been clearly established. Vascular endothelial growth factor is an important part of bone formation. In the literature, although the effects of VEGF on bone metabolism were investigated by different studies, there are very rare studies analysing the association between osteoporosis and VEGF. In the present study, our objective was to investigate serum VEGF concentrations in patients with postmenopausal osteoporosis (PMO) and the correlation of serum VEGF levels and bone mineral density (BMD).

Material and methods

This study was performed on 35 PMO patients, and 30 age-matched healthy controls. Serum VEGF concentrations were measured using a quantitative sandwich enzyme immunoassay technique according to the manufacturer''s instructions. Bone mineral density values were determined by dual energy X-ray absorptiometry (DEXA).

Results

Serum VEGF concentrations were statistically significantly lower in PMO patients than in controls (150 ±65 pg/ml, 260 ±135 pg/ml respectively; p = 0.005). A positive correlation was found between serum VEGF concentrations and BMD values (r = 0.63, p = 0.001).

Conclusions

Vascular endothelial growth factor concentrations were decreased in PMO patients and VEGF may play an important role in bone health.     

Expression of vascular endothelial growth factor (VEGF) and its two receptors (VEGF-R1-Flt1 and VEGF-R2-Flk1/KDR) in non-small cell lung carcinomas (NSCLCs): correlation with angiogenesis and survival

The formation of new vessels (angiogenesis) is essential for primary tumour growth and metastasis and is induced by several angiogenic factors, including vascular endothelial growth factor (VEGF). The microvascular density (MVD) in tumours was assessed and the expression of VEGF and its receptors VEGF-R1-Flt1 and VEGF-R2-KDR/Flk1 was investigated in the different cellular compartments in vivo, in order to establish their interrelationship and their prognostic influence. Immunohistochemical study of 69 stage I–II non-small cell lung carcinomas (NSCLCs) was performed on paraffin sections with CD34 antibody to estimate MVD, using a Chalkley eye-piece graticule and VEGF, VEGF-R1, and VEGF-R2 antibodies. There was strong expression of VEGF and its receptors in tumour cells, endothelial cells, and stromal fibroblasts. In tumour cells, the level of VEGF was correlated with that of VEGF-R1 ( p = 0·018) but not that of VEGF-R2. In fibroblasts, high expression of VEGF was correlated with that of VEGF-R1 ( p = 0·0001) and VEGF-R2 ( p = 0·0001). In endothelial cells, expression of VEGF was correlated with that of VEGF-R1 ( p < 0·0001) and VEGF-R2 ( p = 0·04). The level of VEGF in fibroblasts was correlated with that of VEGF-R1 ( p = 0·0028) and VEGF-R2 ( p = 0·01) in endothelial cells. There was no correlation between the level of MVD and that of VEGF or VEGF-R1 or VEGF-R2. Neither the level of MVD, nor the level of expression of VEGF and VEGF receptors in any compartment influenced the patient's survival. In conclusion, although angiogenesis is essential for tumour growth, this study failed to demonstrate that MVD, VEGF, VEGF-R1, and VEGF-R2 are prognostic markers for stage I–II NSCLC. VEGF, however, might act as a direct autocrine growth factor for tumour cells via VEGF-R1 and angiogenesis could be promoted in a paracrine loop, where VEGF is produced by fibroblasts and tumour cells and then binds to endothelial cells via induced VEGF receptors. VEGF and its receptors thus appear as relevant therapeutic targets in NSCLC. Copyright © 1999 John Wiley & Sons, Ltd.     

Altered ratios of pro‐ and anti‐angiogenic VEGF‐A variants and pericyte expression of DLL4 disrupt vascular maturation in infantile haemangioma

Infantile haemangioma (IH), the most common neoplasm in infants, is a slowly resolving vascular tumour. Vascular endothelial growth factor A (VEGF‐A), which consists of both the pro‐ and anti‐angiogenic variants, contributes to the pathogenesis of IH. However, the roles of different VEGF‐A variants in IH progression and its spontaneous involution is unknown. Using patient‐derived cells and surgical specimens, we showed that the relative level of VEGF‐A₁₆₅b was increased in the involuting phase of IH and the relative change in VEGF‐A isoforms may be dependent on endothelial differentiation of IH stem cells. VEGFR signalling regulated IH cell functions and VEGF‐A₁₆₅b inhibited cell proliferation and the angiogenic potential of IH endothelial cells in vitro and in vivo. The inhibition of angiogenesis by VEGF‐A₁₆₅b was associated with the extent of VEGF receptor 2 (VEGFR2) activation and degradation and Delta‐like ligand 4 (DLL4) expression. These results indicate that VEGF‐A variants can be regulated by cell differentiation and are involved in IH progression. We also demonstrated that DLL4 expression was not exclusive to the endothelium in IH but was also present in pericytes, where the expression of VEGFR2 is absent, suggesting that pericyte‐derived DLL4 may prevent sprouting during involution, independently of VEGFR2. Angiogenesis in IH therefore appears to be controlled by DLL4 within the endothelium in a VEGF‐A isoform‐dependent manner, and in perivascular cells in a VEGF‐independent manner. The contribution of VEGF‐A isoforms to disease progression also indicates that IH may be associated with altered splicing. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Cyclooxygenase-2 and vascular endothelial growth factor in chronic hepatitis,cirrhosis and hepatocellular carcinoma

Background/Aims

Cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are up-regulated in hepatocellular carcinoma (HCC). To investigate the levels of COX-2 and VEGF expression in chronic hepatitis (CH), cirrhosis, and HCC.

Methods

The immunohistochemical expressions of COX-2 and VEGF were evaluated in tissues from patients with CH (n=95), cirrhosis (n=38), low-grade HCC (LG-HCC; n=6), and high-grade HCC (HG-HCC; n=29).

Results

The COX-2 expression scores in CH, cirrhosis, LG-HCC, and HG-HCC were 3.3±1.9 (mean±SD), 4.2±1.7, 5.5±1.0, and 3.4±2.4, respectively (CH vs. cirrhosis, P=0.016; CH vs. LG-HCC, P=0.008; LG-HCC vs. HG-HCC, P=0.004), and the corresponding VEGF expression scores were 0.9±0.8, 1.5±0.7, 1.8±0.9, and 1.6±1.1 (CH vs. cirrhosis, P<0.001; CH vs. LG-HCC, P=0.011; LG-HCC vs. HG-HCC, P=0.075). Both factors were correlated with the fibrosis stage in CH and cirrhosis (COX-2: r=0.427, P<0.001; VEGF: r=0.491, P<0.001). There was a significant correlation between COX-2 and VEGF in all of the tissue samples (r=0.648, P<0.001), and between high COX-2 and VEGF expression scores and survival (COX-2: P=0.001; VEGF: P<0.001).

Conclusions

The expressions of both COX-2 and VEGF are significantly higher in cirrhosis and LG-HCC than in CH. High COX-2 and high VEGF expressions are associated with a high survival rate.     

Expression of vascular endothelial growth factor in renal cell carcinomas

Vascular endothelial growth factor (VEGF) is an angiogenic factor that may be involved in tumor growth and metastasis. Only a few data concerning the role of VEGF in renal cell carcinomas (RCCs) are available, and no studies have yet evaluated its prognostic value. The aim of the present study was to assess VEGF expression in a large series of renal tumors with a long follow-up, correlated with the usual histoprognostic factors and survival. VEGF immunostaining was performed on formalin-fixed, paraffin-embedded archival tissue from 74 renal carcinomas (62 conventional renal cell and 12 papillary carcinomas). Positivity of immunostaining was semi-quantitatively scored by two pathologists. Angiogenesis was evaluated by immunostaining with anti-CD34 antibodies on serial sections. Cytoplasmic VEGF expression was detected in tumor cells in 35% (26/74) of RCCs, including 18 out of the 62 (29%) conventional RCCs and 8 out of the 12 (67%) papillary carcinomas (P=0.02). In the group of conventional RCCs, VEGF expression was positively correlated with both nuclear grade (P=0.05) and size of the tumor (P=0.05). Furthermore, a significant correlation was observed between VEGF expression and microvascular count (P=0.04). Finally, cumulative survival rate was significantly lower in the group of patients with conventional RCCs expressing VEGF (log rank test, P=0.01). In the Cox model, VEGF expression was a significant independent predictor of outcome, as well as stage and nuclear grade. This study suggests that VEGF is involved in angiogenesis in conventional RCCs and appears to be a potential prognostic factor in these tumors. Received: 9 July 1999 / Accepted: 18 October 1999     

Effects of high-altitude exposure on vascular endothelial growth factor levels in man

Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen and permeability factor that is inducible by hypoxia. Its contribution to high-altitude illness in man is unknown. We measured VEGF levels in 14 mountaineers at low altitude (490 m) and 24 h after their arrival at high altitude (4,559 m). At high altitude, VEGF increased from [mean (SEM)] 32.5 (9.2) to 60.9 (18.5) pg·ml^–1 (P<0.004) in the arterial blood, and from 15.9 (2.9) to 49.3 (15.9) pg·ml^–1 (P=0.0001) in the mixed venous blood. Whereas at low altitude venous and arterial VEGF levels were not statistically different from each other (P=0.065), the VEGF concentration was significantly lower in venous than in arterial blood samples at high altitude (P=0.004). The pulmonary capillary VEGF concentration remained unchanged at high altitude [14.8 (2.5) vs 17.1 (5.4) pg·ml^–1, P=0.85]. VEGF levels in the nine mountaineers who developed symptoms of acute mountain sickness (AMS), and in the six subjects who had radiographic evidence of high-altitude pulmonary edema were similar to those in subjects without symptoms. VEGF was not correlated with either AMS scores, mean pulmonary arterial pressures, arterial partial pressure of O₂, or alveolar-arterial O₂ gradients. We conclude that VEGF release is stimulated at high altitude, but that VEGF is probably not related to high-altitude illness. Electronic Publication     

巢蛋白和血管内皮生长因子在脑胶质瘤患者中的表达

目的:探讨巢蛋白和血管内皮生长因子(VEGF)在脑胶质瘤患者中的表达。方法:应用免疫组织化学法检测低级别人脑胶质瘤20例(低级别组)、高级别人脑胶质瘤23例(高级别组)和正常人30例(对照组)脑组织的巢蛋白表达及用酶联免疫吸附法检测血清VEGF在各组人群中的表达水平。结果:人脑组织巢蛋白的阳性细胞数在对照组、低级别组和高级别组分别为5.15±0.37、8.20±1.32和9.65±1.47,三组之间差异均有统计学意义(P﹤0.05);血清VEGF浓度在对照组、低级别组和高级别组分别为(134.05±21.57)pg/ml、(411.75±11.29)pg/ml和(456.23±18.34)pg/ml,三组之间差异均有统计学意义(P﹤0.05);并且脑胶质瘤患者血清VEGF浓度和其脑组织nestin的表达成正相关(r=0.363,P<0.05)。结论:人脑胶质瘤的分级越高,nestin和VEGF的表达就越强,两者均可成为判断脑胶质瘤患者预后的指标。     

The effect of epidermal growth factor on vascular endothelial growth factor secretion by endometrial stromal cells

Endometrial stromal cells undergo morphological and functional changes to facilitate oocyte implantation under regulation of various hormones and growth factors. We studied physiological induction by epidermal growth factor (EGF) of vascular endothelial growth factor (VEGF) in these cells. In human endometrial stromal cells, the effect of EGF, genistein, tryphostin AG1478 (a tyrosine kinase inhibitor), and wortmannin (a phosphatidylinositol 3-kinase inhibitor) on production of VEGF was examined: Total RNA was extracted and VEGF mRNA expression was quantified by Northern analysis. EGF induced production of VEGF by stromal cells in a time-dependent manner; the effect became significant after 12 h and increased further between 24 and 48 h (P<0.05). Dose dependency was also significant (P<0.01). Genistein, tryphostin AG1478, and wortmannin partially suppressed the increase in production induced by EGF (P<0.01, P< 0.01, P<0.01), respectively. Production of EGF by fertilized oocytes and trophoblasts has been reported in early pregnancy. VEGF is believed to be induced by EGF through mechanisms involving tyrosine kinase and phosphatidylinositol 3-kinase. The increase in VEGF may contribute to neovascularization that promotes proliferation of endometrium and placentation. Received: 6 September 2001 / Accepted: 21 May 2002     

Effect of intravitreal bevacizumab on vascular endothelial growth factor expression in patients with proliferative diabetic retinopathy

Purpose

To investigate the effect of bevacizumab (Avastin; Genentech, San Francisco, CA, USA) on vascular endothelial growth factor (VEGF) expression and inflammation in fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR).

Materials and Methods

Fibrovascular membranes from 19 eyes of 18 patients with PDR were studied using immunohistochemistry and analyzed in the following 3 groups; group 1: 4 inactive PDR eyes, group 2: 10 active PDR eyes treated preoperatively with adjunctive intravitreal bevacizumab, group 3: five active PDR eyes not treated preoperatively with bevacizumab. Immunohistochemical staining for VEGF, CD31 and CD68 were done.

Results

The immunoreactivity to VEGF and CD 31-positive blood vessels was significantly higher in membranes from group 3 than group 1 (p = 0.007 for VEGF, 0.013 for CD 31-positive vessels). Intravitreal bevacizumab caused a reduction in VEGF expression and vascular densities in 4 out of 10 (40%) excised membranes from eyes with PDR. However, six membranes (60%) in group 2 still demonstrated relatively strong VEGF expression and high vascular density. Infiltration of macrophages was observed in 16 out of the 19 membranes, and the density of macrophages was increased in group 2 compared with group 1 (p = 0.043).

Conclusion

Intravitreal bevacizumab injections caused some reduction in VEGF expression and vascular densities in a limited number of active PDR patients. A single intravitreal bevacizumab injection may not be enough to induce complete blockage of VEGF and pathologic neovascularization in active PDR patients. Repeated injections, panretinal photocoagulation and/or PPV may be necessary following intravitreal bevacizumab to reinforce the anti-VEGF effect of the drug.     

Expression of vascular endothelial growth factor in exuberant tracheal granulation tissue in children

Prolonged tracheotomy and endotracheal intubation often induce symptoms of airway obstruction and delay decannulation and extubation. Bronchoscopic examination of patients undergoing these treatments usually shows the presence of exuberant (pseudopapillary or nodular) granulation tissue occupying the airway lumen. An immunohistochemical analysis was undertaken of vascular endothelial growth factor (VEGF) expression in exuberant tracheal granulation tissue (n=17) obtained from children treated with prolonged tracheotomy or endotracheal intubation. Increased levels of VEGF protein and mRNA were expressed mainly by tracheal epithelial cells that migrated to cover the granulation tissue and partly by pericapillary macrophages in this tissue, whereas normal tracheal epithelium did not express VEGF. The VEGF expression level correlated significantly with the severity of the exuberant granulation tissue response (p=0·0018). As VEGF induces angiogenesis and vascular permeability, characteristics of granulation tissue, and plays a pivotal role in granulation tissue development, enhanced VEGF expression may be involved in the development of exuberant tracheal granulation tissue. Copyright © 1999 John Wiley & Sons, Ltd     

Apelin and vascular endothelial growth factor are associated with mobilization of endothelial progenitor cells after acute myocardial infarction

This study was designed to determine the levels of early endothelial progenitor cells(EPCs),apelin,vascu-lar endothelial growth factor(VEGF) and stromal cell-derived growth factor-1(SDF-1) after acute myocardial infarction(AMI),and to investigate the relationships between these cytokines and early EPCs.Early EPCs,de-fined as CD133+,KDR+,and CD34+ cells,were quantified by flow cytometry.The levels of early EPCs and those cytokines in AMI patients were significantly different from those with coronary artery disease or controls(P < 0.05).Plasma apelin levels were inversely correlated with Gensini score and early EPCs(both P < 0.01).Early EPCs,VEGF and SDF-1 showed different patterns of changes in AMI patients during the first 24 h.The trend in the change of early EPCs was proportionally correlated with that of VEGF(P < 0.05).AMI patients exhibited in-creased early EPCs with remarkably decreased apelin levels and enhanced VEGF levels.     

血管内皮生长因子在子宫内膜异位症发病中的作用

目的探讨血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)在子宫内膜异位症(endometriosis,EM)发病中的作用。方法应用免疫组织化学方法并结合图像分析技术。结果正常子宫内膜和EM在位内膜腺上皮细胞的VEGF随月经周期呈现规律性变化,分泌期腺上皮VEGF蛋白表达量显著高于增殖期(P<0.05)。在增殖期,EM在位子宫内膜腺上皮VEGF的表达与正常子宫内膜相比无明显差别,但在分泌期,EM在位子宫内膜腺上皮细胞中VEGF的表达强度明显高于正常子宫内膜(P<0.01)。EM在位内膜腺上皮的VEGF含量显著高于同组卵巢子宫内膜异位囊肿的异位腺上皮(P<0.01)。结论表明VEGF的表达异常与EM的发病有关。     

Pancreatic head carcinoma and vascular endothelial growth factor (VEGF-A) concentration in portal blood: its association with cancer grade,tumor size and probably poor prognosis

Introduction

Vascular endothelial growth factor (VEGF) is overexpressed in pancreatic cancer. Although VEGF has been shown to be a probable marker for poor prognosis, the VEGF concentration in portal blood has not yet been clinically reported in pancreatic ductal adenocarcinoma (PDAC). The aim of the study was to measure VEGF-A portal blood concentration in patients with PDAC and to evaluate its performance as a prognostic marker.

Material and methods

Thirty-six consecutive patients out of 57 operated on for pancreatic head lesion with pathologically verified diagnosis of PDAC were enrolled in this study. We evaluated the VEGF concentration in portal blood samples obtained intraoperatively and associated their values with tumor size, stage, grade and survival.

Results

The portal VEGF-A concentration was associated with tumor grade (G1: 80.52 ±43.05 vs. G2: 185.39 ±134.98, p = 0.006, G2: 185.39 ±134.98 vs. G3: 356.46 ±229.12, p = 0.08), and there was a positive correlation with tumor size (r = 0.42, p < 0.05). In the multivariate regression analysis high levels of VEGF-A were not correlated with poor survival (HR = 5.22, 95% CI = –0.6457 to 3.9513, p = 0.19).

Conclusions

The portal VEGF-A concentration is associated with tumor grade and size. The correlation of portal VEGF-A with poor survival is not clear and needs further investigation.     

血管内皮生长因子及其可溶性血管内皮生长因子受体-1水平与胎儿出生体重

目的本研究通过对比血管内皮生长因子(VEGF)、可溶性血管内皮生长因子受体-1(sFlt-1)水平差异与新生儿出生体重的关系,以探讨其在胎儿出生体重发生中的作用。方法采用免疫组织化学法检测40例分娩正常出生体重儿组(AGA组)、30例高出生体重儿组(LGA组)及30例低出生体重儿组(SGA组)胎盘组织中VEGF、sFlt-1的表达水平。结果①LGA组胎盘组织中VEGF的表达高于AGA组,sFlt-1的表达水平低于AGA组,差异有统计学意义(χ2=21.17,P<0.01)。SGA组胎盘组织中VEGF的表达低于AGA组,sFlt-1的表达水平高于AGA组,差异有统计学意义(χ2=8.44,P=0.04)。②胎盘组织中VEGF的表达水平与胎儿出生体重呈正相关(r=0.427,P<0.01),胎盘组织中sFlt-1的表达水平与胎儿出生体重呈负相关(r=-0.569,P<0.01)。结论孕妇胎盘组织中VEGF及sFlt-1表达水平的变化可能与胎儿出生体重有关。     

Intravenous administration of vascular endothelial growth factor improves cardiac performance and inhibits cardiomyocyte apoptosis

This study investigated the effects of vascular endothelial growth factor (VEGF) intravenous administration on cardiac performance and cardiomyocyte apoptosis in a rat model of acute myocardial infarction. Left coronary artery ligation produced extensive myocardial infarction in 48 rats and sham operated in 24 animals. Twenty-four hours after surgery, the rats were randomized to receive VEGF₁₆₅–heparin (treated group) or heparin–saline (control group) treatment. The sham-operated animals were also to receive VEGF₁₆₅–heparin (sham group) treatment. VEGF₁₆₅ (2 μg/ml) with heparin (50 U) or heparin–saline (50 U/ml) was administered daily via the tail vein for 7 and 14 days. Fifty-eight rats survived and included in the study. There were not significant effects of VEGF on hemodynamic parameters in sham animals. As compared with control animals at 9 days after ligation (with 10 rats for each group), rats treated with VEGF had significantly higher maximum rate of left ventricular pressure rise (+dP/dt_max) or fall ( ? dP/dt_max) and microvessel counts, and significantly lower left ventricular end-diastolic pressure (LVEDP) and infarct size. At 16 days after surgery (12, 7 and 9 rats in sham, control and treated groups; respectively), VEGF treatment significantly increased mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), ± dP/dt_max and microvessel counts, and significantly decreased LVEDP and infarct size. VEGF treatment significantly inhibited cardiomyocyte apoptosis and the expression of p53, Fas and Bax protein, and increased the expression of Bcl-2 protein in myocardium at 9 days after myocardial infarction.     

Plasma levels and skin-eosinophil-expression of vascular endothelial growth factor in patients with chronic urticaria

Background:  Although chronic urticaria (CU) is often regarded as autoimmune in nature, only less than 50% of sera from CU patients contain histamine-releasing autoantibodies. This suggests that other factors may contribute to its pathogenesis. We evaluated the possible involvement of vascular endothelial growth factor (VEGF), one of the major mediators of vascular permeability, in CU.
Methods:  Eighty consecutive adult patients with CU and 53 healthy subjects were studied. VEGF and prothrombin fragment F₁₊₂ were measured by enzyme immunoassays. Autologous plasma skin test (APST) was performed in CU patients and, in six of them, skin biopsy specimens were taken from wheals to evaluate the immunohistochemical expression of VEGF and eosinophil cationic protein (ECP).
Results:  Plasma VEGF concentrations were higher in CU patients (8.00 ± 0.90 pmol/l) than in controls (0.54 ± 0.08 pmol/l) ( P  =   0.0001) and tended to parallel both the severity of CU and to correlate with F₁₊₂ levels. APST was positive in 85.1% of patients. VEGF concentration was significantly higher in APST-positive than in APST-negative patients ( P  =   0.0003). Immunohistochemically, all specimens from patients with CU showed a strong expression of VEGF ( P  =   0.002) that colocalized with ECP, a classic eosinophil marker.
Conclusions:  VEGF plasma levels are elevated in CU and parallel the disease severity. This supports a possible role of this molecule in CU pathophysiology. Eosinophils are the main cellular source of VEGF in CU lesional skin.