血管内皮生长因子预防血管成形术后再狭窄的机理

为探讨血管内皮生长因子预防血管成形术后再狭窄的机理 ,构建含人血管内皮生长因子 165基因的重组腺病毒 ,感染体外培养的血管平滑肌细胞 ,将人脐静脉内皮细胞和血管平滑肌细胞分别分成对照组、H2 O2 处理组和H2 O2 +血管内皮生长因子处理组 ,采用WST 1比色法、原位末端标记法及流式细胞术检测各组细胞光密度值和凋亡发生情况。结果发现 ,人脐静脉内皮细胞中 ,与对照组和H2 O2 +血管内皮生长因子处理组比较 ,H2 O2 处理组光密度值降低 ,凋亡细胞明显增加 ;血管平滑肌细胞中上述改变相反。提示H2 O2 能促进平滑肌细胞增殖 ,诱导内皮细胞凋亡 ,抑制内皮细胞增殖及平滑肌细胞凋亡 ,促进再狭窄的发生 ,而血管内皮生长因子能拮抗H2 O2 的作用 ,有利于再狭窄的防治 ,为血管内皮生长因子预防再狭窄提供新的理论依据     

血管内皮生长因子基因预防冠心病介入治疗术后再狭窄的研究进展

血管内皮生长因子 (VEGF)基因在预防冠心病介入治疗 (PCI)术后再狭窄方面已经展现出良好的应用前景。本文就VEGF基因在预防PCI术后再狭窄中的机制、载体的选择、导入途径、实验及临床研究进展、存在的问题等作一综述。     

携带血管内皮生长因子的蛋白涂层支架预防冠状动脉球囊扩张后再狭窄的预防

目的 :评价蛋白涂层支架携带血管内皮生长因子 (VEGF)预防冠状动脉成形术后再狭窄的效果。方法 :金属支架涂层为胶联明胶制成。应用标准球囊导管技术 ,将包被有VEGF的涂层支架置入小型猪 (n =10 )冠状动脉前降支中段 ,以相同方法置入单纯蛋白涂层支架作为对照组 (n =10 ) ,支架与血管直径之比为 1.1～ 1.3∶1。结果 :在支架置入后 3个月时冠状动脉造影显示 :VEGF组无再狭窄发生 ,而对照组均发生显著的再狭窄。组织病理学形态分析结果显示 :VEGF组新生内膜面积 (1.8± 0 .6 )mm2 ,平均百分狭窄面积 (2 5 .9± 6 .5 ) % ,平均管腔狭窄百分数 (40 .4± 13.7) % ,均较对照组〔分别为 (2 .6± 0 .7)mm2 ,P <0 .0 5 ;(93.1± 11.5 ) % ,P <0 .0 1;(88.2± 14 .4 ) % ,P <0 .0 1〕小 ;内膜面积 /中膜面积比值 ,治疗组较对照组减少了 5 5 .3%。结论 :在小型猪模型使用蛋白涂层包被VEGF支架 ,能预防内膜过度增殖 ,从而预防再狭窄的发生。     

血管再内皮化与血管成形术后再狭窄的防治进展

经皮冠状动脉介入治疗已成为治疗冠状动脉粥样硬化性心脏病(冠心病)的重要手段,但术后再狭窄仍是冠心病介入治疗的难题。本文从内皮细胞损伤和功能障碍与再狭窄的关系及改善内皮细胞功能、促进内皮细胞生理性恢复,从而预防再狭窄方面所取得的成果作一综述。     

血管内皮生长因子与动脉粥样硬化

血管内皮生长因子(VEGF)因其潜在的治疗前景引起了国内外的广泛关注。然而,近年来研究发现VEGF可促进动脉粥样硬化的发生和发展。文章就VEGF的分子特征、受体、表达调控、功能及其与动脉粥样硬化的关系作了综述。     

血管内皮生长因子调节内皮祖细胞生物学功能

目的研究血管内皮生长因子（VEGF）对体外培养骨髓源性内皮祖细胞（EPCs）数量及增殖、迁移、黏附功能的影响及机制初探。方法密度梯度离心法获取骨髓单个核细胞,FITC-荆豆凝集素I、DiI-乙酰化低密度脂蛋白荧光双染鉴定。单个核细胞培养7d后分为对照组和VEGF干预组。VEGF干预组加入不同浓度VEGF（25,50,75,100μg／L）培养48h,分别采用四氮唑溴盐比色法、改良的Boyden小室和黏附能力测定观察EPCs的增殖、迁移和黏附能力。RT—PCR法半定量检测VEGF对EPCs内皮型一氧化氮合酶（eNOS）mRNA表达的影响。硝酸还原酶法比色测定VEGF对EPCs分泌一氧化氮的影响。结果VEGF可浓度依赖性地增加EPCs数量并明显促进EPCs的黏附、迁移和增殖能力,与对照组比较差异显著。VEGF可上调EPCseNOSmRNA的表达,促进EPCs分泌一氧化氮。结论VEGF可能通过上调EPCseNOSmRNA的表达影响EPCs部分生物学功能。     

血管内皮生长因子基因治疗促进球囊损伤后内皮细胞再生

血管内皮细胞再生是血管内膜损伤或剥脱后的主要修复方式。本研究在自行成功构建人血管内皮生长因子(ｈＶＥＧＦ1 65)真核表达载体ｐｃＤＮＡ3 ｈＶＥＧＦ1 65基础上 ,将ｈＶＥＧＦ1 65裸质粒ＤＮＡ直接转染球囊损伤后的血管壁 ,观察其对内皮细胞再生以及内膜增生的影响 ,为血管损伤性疾病的防治提供实验依据。1　材料和方法新西兰大白兔 2 4只 ,随机分为治疗组和对照组。所有动物在氯胺酮和安定复合麻醉下 ,制备颈总动脉球囊损伤模型。术后即刻 ,治疗组经扩张导管在损伤的局部动脉腔内给予ｐｃＤＮＡ3 ｈＶＥＧＦ1 65质粒ＤＮＡ 5 0 0 μ…     

血管内皮生长因子与家兔动脉粥样硬化病变进展的关系

为探讨血管内皮生长因子与动脉粥样硬化病变进展的关系。将 5 0只雄性新西兰家兔随机分为二组 :对照组动物喂饲普通颗粒兔饲料 ;动脉粥样硬化模型组动物喂饲含胆固醇 (每只 1.5g d)颗粒兔饲料。分别于实验的第 0、4、8、12周末每组处死兔各 5～ 8只 ,取主动脉 ,采用宏观和微观相结合的方法 ,定性及定量观察病变进展情况。同时用免疫组织化学SP法观察血管内皮生长因子的表达。大体标本及显微标本定性观察均发现 ,随时间延长 ,动脉粥样硬化组兔主动脉的斑块面积逐渐增大 ,斑块厚度增加。显微图象定量测量的结果与定性观察结果一致 ,12周末时 ,斑块平均厚度为 5 .78± 3.75 μm ,明显大于 4周末的 1.2 8± 0 .86 μm ,两者相比 ,差异显著 (P <0 .0 5 ) ,斑块最大厚度可达 2 6 .16 μm。残存管腔面积呈现逐渐狭窄的趋势。免疫组织化学染色发现 ,正常兔主动脉组织中无血管内皮生长因子表达 ,而动脉粥样硬化斑块区内血管内皮生长因子表达呈阳性 ,且随动脉粥样硬化病变进展 ,血管内皮生长因子表达逐渐增强 ,阳性区域的面积也逐渐增大。此结果提示 ,血管内皮生长因子在动脉粥样硬化的发生发展中可能发挥着重要的促进作用。     

人血管内皮生长因子研究进展

血管内皮生长因子(vascular endothelial growth factor,VEGF)为血管内皮细胞特异性肝素结合生长因子,在体内外均可诱导新生血管形成.人VEGF蛋白于1989年分别由美国两个生物科技公司的科学家成功纯化与鉴定,并且其基因序列被成功克隆及测定,证实了VEGF与血管通透因子(VPF)为同一基因编码的同一种蛋白.VEGF为同源二聚体糖蛋白,高度保守,二聚体由分子量各为24 kD的单链以二硫键组成.其单体无活性,N2糖基对其生物效应无影响,但可能在细胞分泌中起作用.近年来关于VEGF的研究较多,研究显示,肿瘤的生长和转移依赖于血管的形成,而VEGF为肿瘤血管生成最有效的促进因子.     

血管内皮生长因子对培养内皮细胞合成一氧化氮的影响

目的 :探讨血管内皮生长因子 （VEGF） /血管渗透因子 （VPF）对内皮细胞 （EC）分泌一氧化氮 （NO）的影响。方法 :将培养的人脐静脉内皮细胞 （HUVEC）随机分为 6组 （n=6 /组 ） :1正常对照组 ;2 VEGF 1ng/ m l;3VEGF 10ng/ m l;4VEGF 10 0 ng/ m l;5低氧组 ;6低氧组 +VEGF 10 0 ng/ m l。采用硝酸还原酶法测定培养液中的 NO2 - ,NO3 -的含量以反映 NO水平。结果 :VEGF促进正常 EC分泌 NO,在一定浓度范围内呈剂量依赖性 ;低氧损伤 EC,使其分泌 NO减少 ;VEGF 10 0 ng/ ml预处理可保护 EC免受低氧损害 ,保持正常分泌 NO的功能。结论 :VEGF能够调节 EC的功能 ,为其促血管形成作用中 EC分裂、增殖、迁移奠定物质基础     

Gene transfer of human vascular endothelial growth factor 165 for prevention of stent restenosis after transjugular intrahepatic portosystemic shunt

OBJECTIVE: To test the hypothesis that locally directed gene transfer of human vascular endothelial growth factor 165 (hVEGF₁₆₅) is able to passivate hepatic venous metallic stents by accelerating endo­thelialization and augmenting the biocompatibility of endovascular stents. METHODS: Complexes of pAdtrackCMV‐hVEGF₁₆₅ and lipofectamine were smeared homogeneously on the surface of the stents coated with poly‐L ‐lysine. Bare stents were used as controls. All stents were implanted into the right hepatic vein by transjugular intrahepatic venous stent deployment. RESULTS: At the end of the first week after implantation, green fluorescence and the expression of the hVEGF₁₆₅ gene were detected in the transferred stent vessels of the treated group, but were not detected in the control group. Scanning electron microscopy revealed that the endothelialization of stents was more pronounced in the treated group than that in the control group. At the end of the eighth week after implantation, quantitative angiography analysis showed the internal diameter of the stent was significantly greater in the treated group than in the control group. The de novo intima, their mean areas and percentage cross‐sectional area narrowing in the treated group were significantly less than those in the control group. Immunohistochemical analysis indicated that the proliferation of vascular smooth muscle cells was more active in the control group than that in the treated group. CONCLUSION: Local gene transfer of hVEGF₁₆₅ can passivate endovascular stents by accelerating stent endothelialization and enhancing their biocompatibility in the hepatic vein, resulting in a reduction of thrombus formation and attenuation of intimal hyperplasia.     

血管内皮细胞生长因子对肾小球内皮细胞通透性的影响

目的 :观察血管内皮细胞生长因子 (VEGF)对肾小球内皮细胞通透性的影响 ,并与脐静脉内皮细胞进行比较分析。　 方法 :采用二室弥散系统检测内皮细胞通透性。肾小球内皮细胞 (MGEC)和人脐静脉内皮细胞(HUVEC)接种于细胞培养嵌套的微孔滤膜 (孔径 0 4 5 μm)上 ,待细胞生长融合后 ,加入不同浓度的VEGF作为处理因素 ,以生物素标记的牛血清白蛋白 (biotin BSA)作为通透性指示剂 ,采用ELISA方法检测不同时间段biotin BSA通过细胞单层的百分数。　 结果 :正常培养条件下 ,生长在滤膜上的MGEC和HUVEC单层的通透性没有明显差异。VEGF可显著增加MGEC和HUVEC的通透性 ,呈剂量和时间依赖性。 1μg/LVEGF作用 12h可使MGEC对白蛋白的通透率增加近 2 5 % (0 31± 0 0 3vs 0 2 5± 0 0 3) ;VEGF浓度达 10 μg/L始显著增加HUVEC通透性 (0 2 8± 0 0 7vs0 2 1± 0 0 4 ) ,且远小于MGEC通透性增加的幅度 (P <0 0 1) ;VEGF浓度达 5 0 μg/L时 ,其增加内皮细胞通透性的作用基本达到饱和。 5 0 μg/LVEGF作用 0 5h即可使MGEC和HUVEC的蛋白通透率分别增加 10 0 % (0 12± 0 0 2vs0 0 6± 0 0 1)和 6 0 % (0 0 8± 0 0 3vs0 0 5± 0 0 1) ,并至少持续到 12h。　 结论 :首次在体外直接证实了VEGF具有增加MGEC     

VEGF与VEGF-C蛋白在胆管癌中的表达及意义

目的探讨VEGF与VEGF-C蛋白在胆管癌的表达及其与临床病理特征的关系。方法采用免疫组化SP法检测49例胆管癌组织中vEGF与VEGF-C叠白的表达。结果胆管癌VEGF和VEGF—C蛋白的表达率分别为65．3％和69．4％。VEGF和VEGF-C蛋白的高表达与胆管癌淋巴结转移及分化程度有关。VEGF与VEGF—C的表达有显著相关性（P＜0．01）。结论VEGF和VEGF—C蛋白的表达与胆管癌侵袭转移有关。     

Clinical significance of vascular endothelial growth factor and hepatocyte growth factor in multiple myeloma

Angiogenesis is a crucial process in the progression of multiple myeloma (MM). Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are multifunctional cytokines that potently stimulate angiogenesis including tumour neovascularization. Serum levels of VEGF and HGF were measured in 52 patients with MM by enzyme-linked immunosorbent assay (ELISA). Serum levels of VEGF and HGF were elevated in MM patients compared with healthy controls (VEGF: mean 0.31 ng/ml and 0.08 ng/ml respectively, P < 0.01; HGF: mean 2.17 ng/ml and 0.45 ng/ml, respectively, P < 0.001). In serial samples taken after chemotherapy, serum VEGF and HGF levels were correlated with M-protein levels. Serum levels of VEGF were higher in patients with extramedullary plasmacytomas than in patients without them (P < 0.05). They were also significantly higher in a group of patients who showed poor response to chemotherapy (P < 0.01). Serum levels of HGF were higher in patients with complications such as anaemia, hypercalcaemia and amyloidosis than in patients without these complications (P < 0.01, P < 0.05, P < 0.05 respectively). Both serum VEGF and HGF levels were significant predictors of mortality (P = 0.01, P = 0.02, respectively, log-rank test). The present study demonstrated that serum levels of VEGF and HGF are significantly elevated and dependent on the severity of MM, suggesting that measurement of VEGF and HGF may be useful for assessing disease progression and for predicting the response to chemotherapy in MM patients.     

The crucial role of vascular permeability factor/vascular endothelial growth factor in angiogenesis: a historical review

Angiogenesis is a biological process by which new capillaries are formed and it occurs in many physiological and pathological conditions. It is controlled by the net balance between molecules that have positive and negative regulatory activity and this concept had led to the notion of the 'angiogenic switch', depending on an increased production of one or more of the positive regulators of angiogenesis. Numerous inducers of angiogenesis have been identified and this review offers a historical account of the relevant literature concerning the discovery of one of the best characterized angiogenic factors, namely vascular endothelial growth factor (VEGF)/vascular permeability factor. Moreover, different strategies, designed to stimulate and to inhibit VEGF production in the context of several potential therapeutical implications, are discussed.     

血管、淋巴管内皮生长因子在胰腺癌中的表达

研究血管内皮生长因子(VEGF)在胰腺癌中的表达及意义,采用:Northern blot分析法检测正常胰腺组织和胰腺癌组织中VEGF-A、c mRNA的表达;采用免疫组织化学染色法检测胰腺癌标本中VEGF-A、C蛋白的表达。结果发现胰腺癌组织中VEGF-A和VEGF-C基因的表达分别是正常胰腺组织中的3.0和3.6倍;免疫组织化学染色法显示胰腺癌组织中VEGF-A和VEGF-C的阳性率分别为50％和80％;胰腺癌细胞VEGF-A的表达与肿瘤大小呈正相关,VEGF-C的表达与淋巴结转移呈正相关,均有统计学意义(P<0.05),而VEGF-A与VEGF-C表达无关联。胰腺癌非同步联合表达血管和淋巴管内皮生长因子,前者与肿瘤大小、局部范围相关联,后者与淋巴结转移相关联。     

High expressions of vascular endothelial growth factor and platelet-derived endothelial cell growth factor predict poor prognosis in alpha-fetoprotein-negative hepatocellular carcinoma patients after curative resection

Purpose  To evaluate the prognosis value of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) in alpha-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) patients after curative resection. Methods  Tumor tissue microarrays (TMAs) were used to detect the expressions of VEGF and PD-ECGF in consecutive 162 AFP-negative HCC patients undergoing curative resection between 1997 and 2000 in our institute. Clinicopathologic data for these patients were evaluated. The prognostic significance was assessed using Kaplan–Meier survival estimates and log-rank tests. Multivariate study with Cox’s proportional hazard model was used to evaluate the prognosis-related aspects. Results  The positive rates of VEGF and PD-ECGF in tumor tissues were 59.9% (97/162) and 62.3% (101/162), respectively. Univariate analysis showed that VEGF and PD-ECGF were prognostic factors for relapse-free survival (P = 0.034 and P = 0.033, respectively). Multivariate analyses demonstrated that the co-index (VEGF/PD-ECGF) was an independent prognostic factor for overall survival and relapse-free survival (P = 0.002 and P = 0.000, respectively). Conclusion  The co-index of VEGF and PD-ECGF is a promising independent predictor for recurrence and survival of AFP-negative HCC patients after curative resection. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. J. Hu, Y. Xu and Z.-Z. Shen have contributed equally to this work.