碱性成纤维细胞生长因子预防球囊成形血管再狭窄

目的 :探讨实验性兔髂动脉粥样硬化狭窄模型于血管成形后 ,给予碱性成纤维细胞生长因子 (b FGF) ,对改善血管内皮功能及对再狭窄的预防作用。方法 :建立髂动脉狭窄模型兔 6 0只 ,2 0只用于成形前 (10只 )和成形后即刻 (10只 )管腔面积的组织学分析 ,余 40只随机分成 b FGF组和对照组 ,于血管成形后 4周两组兔均处死 ,行体外血管反应性测试和管腔面积的组织学分析。结果 :由乙酰胆碱诱导的内皮依赖性最大舒张反应 (Emax)b FGF组 [(41± 8) % ]大于对照组 [(12± 9) % ],P <0 .0 5 ;由硝普钠 (SNP)诱导的内皮非依赖性血管 Emax b FGF组 [(88± 7) % ]大于对照组 [(6 6± 5 ) % ],P <0 .0 5 ;血管成形后 4周对照组腔面积 [(0 .5 4± 0 .2 6 ) mm2 ]小于b FGF组 [(1.0 8± 0 .32 ) mm2 ],P <0 .0 5 ,比成形后即刻 [(1.2 0± 0 .2 8) mm2 ]狭窄 5 5 %。结论 :实验性髂动脉粥样硬化狭窄模型兔于血管成形后给予 b FGF,在促进内皮依赖性及非依赖性血管舒张功能恢复的同时 ,有预防成形血管近期再狭窄发生的作用     

血管内皮生长因子的表达与胃癌浸润和转移的关系

目的　研究血管内皮生长因子165(VEGF)mRNA在胃癌中的表达 ,探讨VEGF与胃癌浸润和转移的关系。方法　采用RT PCR方法 ,对 31例胃癌及非癌组织手术标本中VEGF165mRNA的表达进行相对定量研究。结果　胃癌组织中VEGF165mRNA表达的平均相对量 (1.12 5± 0 .35 6 )明显高于非癌组织的表达量 (0 .76 0± 0 .2 78,P <0 .0 5 ) ,其中淋巴结转移组 (1.2 19± 0 .377)和Ⅲ、Ⅳ期组 (1.2 6 2±0 .386 )分别高于无淋巴结转移组 (0 .92 7± 0 .2 0 5 )和Ⅰ、Ⅱ期组 (0 .934± 0 .194 ,P均 <0 .0 5 )。VEGF高表达者中淋巴结转移率为 83.3% ,Ⅲ和Ⅳ期占 77.8% ,均明显高于VEGF低表达者的 4 6 .2 %和 33.8%(P <0 .0 5 )。结论　胃癌组织中有VEGF的高表达 ,VEGF的表达在胃癌浸润和转移过程中发挥重要作用。     

血管内皮生长因子及其受体随增龄在大鼠肾组织内表达的研究

目的　研究血管内皮细胞生长因子 (VEGF)及其受体Flt 1和Flk 1在大鼠肾组织内的表达及随增龄变化 ,探讨它们在肾脏衰老过程中的作用。　方法　应用 3、12、2 4月龄 (各 7只 )大鼠肾组织石蜡切片进行常规病理及免疫组织化学染色 ,定量分析肾组织内微血管变化及VEGF、Flt 1和Flk 1表达变化。应用逆转录聚合酶链反应技术 (RT PCR)检测肾组织内VEGF AmRNA的表达。　结果　 2 4月龄组与 3月龄组相比肾小球面积增大〔(15 6 35± 10 2 2 ) μm2 vs(72 0 5± 496 ) μm2 ,P <0 0 1〕 ,肾小球内毛细血管袢腔面积与肾小球面积百分比减少 (46 76 %± 4 91%vs 6 3 75 %±6 0 2 % ,P <0 0 1) ,肾小管周围毛细血管数量减少 (9 8± 2 6vs 14 7± 3 1,P <0 0 1) ;肾小球内VEGF阳性细胞数增多 (9 3± 2 4vs 6 4± 1 6 ,P <0 0 5 ) ;集合管中VEGF的表达则明显减少(9 35 %± 2 10 %vs 15 2 3%± 3 2 2 % ,P <0 0 5 ) ;Flk 1在肾小球血管袢上表达增加 (9 17%±2 0 2 %vs 1 0 3%± 0 35 % ,P <0 0 1) ,而Flt 1和Flk 1在肾小管上表达则明显减少 (7 6 4%±3 0 2 %vs 15 36 %± 2 5 4% ,2 48%± 0 86 %vs 9 0 1%± 2 6 3% ,P <0 0 1)。 2 4月龄组VEGF AmRNA较其他两组减少 (P <0 0 5 )。　结论　VEGF、Flk     

类风湿关节炎患者血管内皮生长因子mRNA的表达

目的　以类风湿关节炎 (RA)患者血管内皮生长因子 (VEGF)在外周血单个核细胞(PBMC)mRNA的表达为研究对象 ,探讨VEGF与RA病情的关系和VEGF在RA中的病理作用。方法　应用半定量RT PCR方法检测 18例RA患者和 12名健康人PBMCVEGFmRNA的表达。结果　①RA患者和健康人PBMCVEGFmRNA的表达以与内参照 β Actin的比值计算 ,RA组 (6 4±6 4 )显著高于正常对照组 (1 5± 1 0 ) ,P =0 0 0 5。②晚期RA患者的PBMC表达VEGFmRNA (8 4± 8 7)高于早期患者 (4 5± 2 0 ) ,P =0 0 2 5 ;且高度活动组的患者 (11 0± 9 8)高于轻、中活动组的患者 (4 2± 2 0 ) ,P =0 0 0 2。结论　①RA患者PBMCVEGF的mRNA表达增强 ;②RA患者PBMC的VEGFmRNA表达在晚期患者和高活动性患者增强更显著。本研究提示 ,VEGF作为重要的血管增生的促进因子参与到RA的病理过程中     

重组人碱性成纤维细胞生长因子对缺血心肌血管结构的作用观察

目的　观察重组人碱性成纤维细胞生长因子 (rhb FGF)对缺血心肌血管结构的作用。方法　建立兔急性心肌梗死模型 ,将 rhb FGF直接四点注射入兔缺血心肌内 ,通过病理切片图像分析观察缺血心肌血管管壁及管腔变化情况。结果　 rhb FGF组与生理盐水组平均管壁厚度分别为 6周 :(2 0 .70± 9.94 ) μm,(18.88± 9.6 5 ) μm,P>0 .0 5 ;12周 :(2 9.87± 12 .96 )μm,(18.13± 11.33)μm,P<0 .0 1;管壁管腔比值分别为 6周 :0 .2 5± 0 .12 ,0 .2 4± 0 .0 2 ,P>0 .0 5 ;12周 :0 .33± 0 .14 ,0 .2 4± 0 .0 9,P >0 .0 5。结论　 rhb FGF促缺血心肌血管新生到一定时期 (可能小于 12周 ) ,血管数量不再增长 ,只是血管管腔增大 ,管壁增厚 ,发生血管重构。     

重组人生长激素对急性心肌梗死大鼠冠状动脉侧支循环的影响

目的 :探讨重组人生长激素 (rh GH)对急性心肌梗死 (AMI)大鼠冠状动脉侧支循环及血管内皮细胞生长因子 (VEGF)、成纤维细胞生长因子 (bFGF)的影响。方法 :5 0只Wistar大鼠经 10 %戊巴比妥钠麻醉后开胸 ,剪开心包腔 ,经左冠状动脉前降支结扎术致其发生AMI ,术后 2 4h存活者 37只被随机分为治疗组 (19只 )和对照组 (18只 )。治疗组以rh GH 0 .2 5IU/kg肌内注射 ,对照组肌内注射同等容积的0 .9%氯化钠溶液 ,3周后处死大鼠 ,开胸经升主动脉向冠状动脉内灌注 4 %多聚甲醛 2 0～ 30min固定心脏 ,心脏标本经切片处理。分别测定血浆和心肌的VEGF、bFGF的量及左室毛细血管密度。结果 :治疗组与对照组在AMI后 3周其血浆bFGF、VEGF浓度均较实验开始时明显增加 (P <0 .0 5 )。治疗组较对照组升高更加显著 ,分别为 (6 8.72± 4 .5 7)∶(35 .6 0±4 .31)和 (4 7.0 5± 5 .13)∶(32 .13± 5 .70 ) (均P <0 .0 5 )。大鼠心肌内bFGF及VEGF治疗组均较对照组高 ,分别为 (79.0 5± 6 .96 )∶(30 .7± 3.4 9)和 (72 .0 5± 6 .73)∶(39.33± 6 .78) (均P <0 .0 1)。血浆bFGF、VEGF的浓度与心肌内毛细血管密度呈正相关 (r分别为 0 .91和 0 .86 ,均P <0 .0 1)。结论 :rh GH能促进AMI大鼠心肌细胞生长因子bFGF和VEGF的表达和分泌     

血管内皮细胞生长因子对小鼠CFU-GM、CFU-E、CFU-S生成的影响

目的 :研究血管内皮细胞生长因子 (VEGF)对小鼠骨髓单个核细胞 (MNC)粒 巨噬细胞系集落形成单位 (CFU GM)、红系集落形成单位 (CFU E)、脾集落形成单位 (CFU S)生成数量的影响。方法 :一部分小鼠骨髓MNC样本在加入或不加入外源性hVEGF的体系中预先培养 2 4h ,分别进行体外造血细胞集落培养和小鼠体内CFU S试验 ,计数CFU GM、CFU E、CFU S集落生成数目 ;另外对剩余骨髓样本不经处理直接在含rhVEGF的体系中进行体外CFU GM、CFU E集落培养 ,观察集落培养体系中添加VEGF对集落生成的影响。结果 :CFU GM、CFU E、CFU S数目分别为 33.2 1± 2 .84、72 .0 0± 4 .5 5和 12 .2 0± 1.32 ,显著高于未处理组 (分别为19.6 0± 2 .10、38.86± 2 .77和 6 .10± 1.5 2 ) (P <0 .0 5 ) ,但均低于正常对照组 (分别为 5 1.97± 2 .4 5、16 4 .2 0± 5 .70和 19.5 0± 2 .4 6 )。外源性hVEGF的存在使VEGF组CFU GM、CFU E产率较正常对照组显著提高 (73.12±3.80∶5 1.39± 2 .6 0 ,198.98± 4 .92∶16 4 .4 0± 5 .32 ) (P <0 .0 5 )。结论 :VEGF不仅对造血细胞集落生成能力具有保护作用 ,还具有促进造血细胞集落生成的作用。     

血管内皮生长因子对急性心肌梗死大鼠心肌细胞凋亡的影响

目的　探讨静脉应用血管内皮生长因子 (VEGF)对急性心肌梗死大鼠心肌细胞凋亡及凋亡相关蛋白P5 3、Fas、Bax和Bcl 2表达的影响。　方法　 3 3只雄性SD大鼠结扎左冠状动脉后 2 4h随机接受VEGF16 5 肝素 (治疗组 )或肝素 生理盐水 (对照组 )治疗。VEGF16 5(2 μg/1ml)加肝素 (5 0U)或肝素 生理盐水 (5 0U/1ml)每天经尾静脉注射 ,共用 7d(治疗组 8只 ,对照组 10只 )和 14d(治疗组 7只 ,对照组 8只 )。于结扎后第 9天和第 16天测定心肌细胞凋亡指数、心肌组织P5 3、Fas、Bax和Bcl 2蛋白的表达。　结果　治疗组的心肌细胞凋亡数量明显少于对照组〔第 9天 :(10± 2 ) %比 (2 8±2 ) % ,P <0 0 1;第 16天 :(6± 2 ) %比 (12± 2 ) % ,P <0 0 5〕 ,VEGF抑制P5 3、Fas和Bax的表达 ,促进Bcl 2的表达。　结论　每天静脉应用VEGF 14d可减少心肌细胞凋亡 ,抑制P5 3、Fas和Bax的表达 ,促进Bcl 2的表达     

血管内皮生长因子、微血管密度与食管鳞癌临床病理及预后的关系

为探讨血管内皮生长因子 (VEGF)、微血管密度 (MVD)与食管鳞癌临床病理和预后的关系 ,对 4 4例原发食管鳞癌、6例食管不典型增生及 10例正常人的食管组织石蜡切片进行血管标记和染色 ,检测 VEGF表达及 MVD。结果显示 ,食管鳞癌患者 VEGF阳性表达率为 6 5 .9% (2 9/ 4 4 ) ,VEGF表达与肿瘤大小、分化程度、淋巴结转移及 TNM分期显著相关 ;MVD与分化程度、淋巴结转移、TNM分期明显相关 ;VEGF表达阳性组 MVD(47.34± 11.5 7条 )明显高于阴性组 (33.73± 11.33条 ) ,VEGF表达与 MVD具有相关性 ;VEGF阴性组和阳性组术后 3年生存率有显著差异 ,高 MVD者和低 MVD者术后 3年生存率有显著差异 (P<0 .0 1)。认为食管鳞癌VEGF表达增强 ,MVD增高 ;VEGF表达在食管鳞癌的生长、浸润和转移过程中起重要作用 ;VEGF和 MVD对于判断食管鳞癌预后有重要参考价值     

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。     

超声评价辛伐他汀的抗兔动脉粥样硬化作用及其机制的探讨

目的应用彩色多普勒超声及声学密度定量技术评价辛伐他汀对兔腹主动脉粥样硬化(AS)的作用,并分析辛伐他汀对AS斑块增殖细胞核抗原(PCNA)和碱性成纤维细胞生长因子(bFGF)表达的影响。方法 30只日本大耳白兔平均随机分为3组:健康对照组(A组),AS模型组(B组),辛伐他汀治疗组(C组)。在食物中加入高脂饲料建立兔动脉粥样硬化模型。16周末测定血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)。超声检测腹主动脉壁结构及血流,测量动脉内膜-中层厚度(IMT)、收缩期血流峰值速度(Vp),同时定量测定动脉壁声学密度值,与病理形态学检查结果相对照,并以免疫组织化学方法分析PCNA和bFGF在斑块中的表达。结果 16周末B、C组血清TC、TG、LDL-C较A组显著增高,C组较B组减低(P<0.05)。超声检查可见B组、C组腹主动脉AS改变,与病理形态学结果一致,IMT较A组显著增高,C组IMT为(0.51±0.11)mm较B组(0.68±0.13)mm减低(P<0.05),C组动脉内中膜声学密度值、内中膜校正回声强度值较B组减低[(32.73±2.46)dB比(42.33±1.84)dB]、(1.25±0.11)比(1.67±0.08)(P<0.05)。C组bFGF、PCNA表达较B组减低,差异有统计学意义(P<0.05)。结论辛伐他汀不仅可以降低血脂水平,还能够减少斑块中bFGF、PCNA表达。超声显像及声学密度定量检测能够准确评价动脉壁形态学及声学密度特征,为临床评估AS进展及消退提供依据。     

心力衰竭患者血清血管内皮生长因子和C-反应蛋白的变化及意义

目的检测心力衰竭(HF)患者血清血管内皮生长因子(VEGF)和C-反应蛋白(CRP)的水平,探讨VEGF在HF发生和发展过程中的作用。方法选取HF患者100例,其中男性53例,女性47例。将慢性HF患者按NY-HA标准进行心功能分级,心功能Ⅱ级为Ⅱ组(37例),心功能Ⅲ~Ⅳ级为Ⅲ组(32例),急性HF患者为Ⅳ组(31例)。测定VEGF及CRP水平,比较各组间VEGF、CRP的变化,并与正常对照组(Ⅰ组,n=35)比较,同时分析VEGF和CRP之间的相关性。分析原发性高血压、高胆固醇血症、糖尿病、及稳定型心绞痛对HF患者VEGF水平的影响。结果(1)Ⅱ~Ⅳ组的VEGF和CRP水平均显著高于Ⅰ组(P均<0.05)。(2)Ⅳ组VEGF水平显著高于Ⅲ组和Ⅱ组(P均<0.05);Ⅱ组和Ⅲ组VEGF水平无显著差异(P>0.05);Ⅲ组CRP水平显著高于Ⅱ组(P<0.05);Ⅳ组和Ⅲ组CRP水平无显著差异(P>0.05)。(3)HF患者血清VEGF与CRP无相关性(r=0.1786,P>0.05)。(4)原发性高血压HF组和血压正常HF组VEGF无显著差异(P>0.05)。高胆固醇HF组和胆固醇正常HF组比较、糖尿病HF组和非糖尿病HF组比较、稳定型心绞痛HF组和不合并心绞痛HF组比较VEGF均无显著差异(P均>0.05)。结论HF患者VEGF及CRP水平显著升高。急性HF组高于慢性HF组.VEGF及CRP水平均随着HF程度的加重而升高。原发性高血压、高胆固醇血症、糖尿病、及稳定型心绞痛对HF患者血清VEGF水平可能无明显影响。     

血管内皮、碱性成纤维细胞生长因子表达与非小细胞肺癌患者生存期的关系

目的 探讨血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)在非小细胞肺癌(NSCLC)中的表达及其与患者生存期的关系。方法 应用免疫组织化学方法检测96例NSCLC组织中VEGF、bFGF蛋白水平的表达，并探讨二者表达与患者生存期的关系。结果 NSCLC中VEGF、bFGF表达阳性率分别为51．0％(49／96)和58．3％(56／96)，二者具有相关性(P=0．041)，与患者生存期之间无统计学意义。结论 VEGF、bFGF在NSCLC血管形成中起重要作用，但不是NSCLC独立的预后因素。     

粒细胞集落刺激因子与动脉粥样硬化对外周血内皮祖细胞数量的影响

目的观察粒细胞集落刺激因子（granuloeyte colony-stimulating factor,G-CSF）与动脉粥样硬化（atherosclerosis,AS）对外周血内皮祖细胞（EPC）的影响。方法将32只雄性新西兰白兔随机分为G组（重组人粒细胞集落刺激因子rhG-CSF50彬d）、G＋AS组（rhG-CSF 50μg/d、高脂饲料）、AS组（高脂饲料）及对照组,每组各8只。4组动物分别于实验前及第1、4、8、12周采血,培养7天后,用荧光显微镜观察鉴定FITC-UEA-1和Dil-acLDL双染色阳性细胞为正在分化的EPC;细胞培养3天后,通过流式细胞仪计数各组PE-CD34、FITC-CD133双阳性细胞为EPC;第12周测血清一氧化氮、血脂水平并做主动脉斑块分析。结果实验前,各组EPC含量均很低;用G-CSF治疗1周,G组及G＋AS组EPC迅速升高（与用药前比较增加了约13倍,P〈0．001）,继续给药G组EPC维持在一个较高水平（第1、4、8、12周比较P〉0．05）;给予高脂饮食后,G＋AS组EPC数量逐渐下降（第4、8周与对照组比较P〈0．001、P〈0．001;第12周与对照组比较P=0．326）;对照组EPC一直处于低水平,AS组EPC数量较对照组低,但两组各周比较P〉0．05。经过12周的高脂喂养,G＋AS组及AS组主动脉均形成了动脉粥样硬化斑块,但G＋AS组斑块面积、斑块／内膜面积均低于AS组（P〈0．01）。第12周G＋AS组及AS组一氧化氮含量均低于G组和对照组（P〈0．001）。结论EPC与动脉粥样硬化关系密切,AS损害内皮,减少EPC,G-CSF对EPC有动员作用,能够增加外周血EPC数量,因而对血管有保护作用,抑制AS进展。     

Concomitant expression of heparin-binding epidermal growth factor-like growth factor mRNA and basic fibroblast growth factor mRNA in myocardial infarction in rats

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is mitogenic and chemotactic for many cell types. HB-EGF is induced in pathological states which require cell mitogenesis and proliferation, including angiogenesis, and has been reported to interact functionally with basic fibroblast growth factor (bFGF). To test our hypothesis that HB-EGF mRNA expression is increased in myocardial infarction, we used Northern hybridization in rats to investigate the expression of HB-EGF and EGF receptor mRNAs expression in the infarct zone compared to the expression of bFGF and FGF receptor mRNAs. We also performed in situ hybridization to identify the cells responsible for HB-EGF mRNA production. HB-EGF mRNA rapidly increased after ligation (mean ± SE, 5.6 ± 0.23-fold increase at 6 hours compared to the preligation heart levels) and reached a maximum level (9.1 ± 0.42-fold increase) around 12 hours. HB-EGF mRNA then gradually decreased on day 1 (5.8 ± 1.0-fold increase), day 2 (3.2 ± 0.94-fold increase) and day 3 (1.9 ± 0.33-fold increase) after ligation. Parallel changes in bFGF mRNA expression were observed (6, 12 hours, days 1, 2 and 3; 3.6 ± 0.42-, 5.3 ± 0.12-, 2.3 ± 0.12-, 1.7 ± 0.03- and 0.95 ± 0.03-fold increase, respectively). EGF receptor (ErbB-1) mRNA was gradually increased on day 2 (2.4 ± 0.53-fold increase), day 7(4.0 ± 0.61-fold increase) and day 14 (7.0 ± 0.61-fold increase). Similarly, FGF receptor (FGF receptor-1) mRNA was gradually increased (days 2, 7 and 14; 1.3 ± 0.13-, 1.5 ± 0.17- and 2.3 ± 0.15-fold increase, respectively). Reperfusion after a 2-hour ligation (too late to salvage myocytes) enhanced HB-EGF (12 hours, 16.8 ± 1.8-fold increase) and bFGF (12 hours, 10.4 ± 1.1-fold increase) mRNA expression. The cells responsible for the increased production of HB-EGF mRNA were shown by in situ hybridization to be surviving myocytes located in the infarct peripheral zone around infarct necrotizing tissue. In conclusion, our results demonstrated a rapid increase in HB-EGF mRNA expression concomitant with an increase in bFGF mRNA expression, suggesting that HB-EGF and bFGF might play some role in the course of pathological changes in the infarct in the early inflammatory phase. Reperfusion at times too late to salvage myocytes accelerated sequential changes in the expression of both HB-EGF and bFGF mRNAs. Received: 16 March 2001, Returned for 1. revision: 23 April 2001, 1. Revision received: 31 July 2001, Returned for 2. revision: 22 August 2001, 2. Revision received: 4 September 2001, Accepted: 6 September 2001     

Levels of vascular endothelial growth factor and hepatocyte growth factor in sera of patients with rheumatic diseases

 Angiogenesis plays an important role in the progression of rheumatic disease. We measured the levels of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in sera from patients with rheumatic diseases and investigated whether these angiogenic factors would be useful in the evaluation of rheumatic diseases. Serum VEGF and HGF levels were determined using ELISA in 128 patients with rheumatic diseases and in 11 healthy controls. Serum VEGF and HGF levels were significantly higher in patients with rheumatic diseases compared to healthy controls [VEGF, 312 ± 20 pg/ml versus 61 ± 8 pg/ml (mean ± SE), P < 0.001; HGF, 935 ± 36 pg/ml versus 413 ± 49 pg/ml, P < 0.01]. Serum VEGF and HGF levels were significantly elevated in patients with adult Still's disease (VEGF, 1021 ± 258 pg/ml; HGF, 1500 ± 295 pg/ml) and were relatively increased in patients with active rheumatoid arthritis (RA) (VEGF, 359 ± 94 pg/ml) and systemic sclerosis (SSc) (VEGF, 356 ± 43 pg/ml; HGF, 1294 ± 224 pg/ml). HGF levels correlated with the clinical course and disease severity in rheumatic disease patients. VEGF levels correlated with the presence of Raynaud's phenomenon (P < 0.05), interstitial lung disease (ILD) (P < 0.05), and serum KL-6 levels (P < 0.01), whereas HGF levels correlated with cryoglobulinemia (P < 0.05), ILD (P < 0.05), serum C-reactive protein (CRP) (P < 0.05), thrombomodulin (P < 0.05), and KL-6 levels (P < 0.05) in rheumatic disease patients. VEGF levels correlated with the skin scores and KL-6 levels in SSc patients and also correlated with the disease activity of RA patients. These data suggest that serum VEGF and HGF levels are related to rheumatic disease activity and the presence of complications. Analysis of VEGF and HGF may be useful in the clinical evaluation of rheumatic disease patients. Received: February 19, 2002 / Accepted: August 13, 2002 Acknowledgment We are grateful to Ms. Aki Nomura for assistance with the ELISA of VEGF and HGF.     

Serum levels of platelet-derived growth factor-BB and vascular endothelial growth factor as prognostic factors for patients with fulminant hepatic failure

Background and Aims: In animal models for acute liver injury, the administration of some angiogenic factors such as vascular endothelial growth factor (VEGF) and granulocyte‐colony stimulating factor (G‐CSF) are shown to reduce liver injury and improve liver proliferative capacity. The aim of the present study was to assess the role of angiogenic factors in fulminant hepatic failure (FHF). Methods: Serum levels of nine angiogenic factors (angiopoietin‐2, follistatin, G‐CSF, hepatocyte growth factor [HGF], interleukin‐8, leptin, platelet‐derived growth factor [PDGF]‐BB, platelet endothelial cell adhesion molecule‐1 and VEGF) were measured using the Bio‐Plex Protein Array System in 30 patients, 17 of whom were diagnosed with FHF, 13 with acute hepatitis (AH), and 20 controls. Results: Serum levels of PDGF‐BB and VEGF were lower in FHF patients than AH patients and controls (PDGF‐BB; 2050 ± 1572 pg/mL vs 4521 ± 2419 pg/mL vs 8506 ± 5500 pg/mL, VEGF; 39 ± 38 pg/mL vs 144 ± 122 pg/mL vs 205 ± 121 pg/mL). By using univariate logistic regression models, serum levels of PDGF‐BB and VEGF were associated with poor outcomes. Serum PDGF‐BB levels were strongly correlated with serum VEGF levels (r = 0.70). Furthermore, serum PDGF‐BB levels were significantly correlated with platelet counts (r = 0.79), PT activity (r = 0.37) and D.Bil/T.Bil ratio (r = 0.50), while serum VEGF levels were significantly correlated with platelet counts (r = 0.68) and PT activity (r = 0.38). Conclusions: We consider that serum levels of PDGF‐BB and VEGF are worth investigating as biomarkers for predicting outcomes of FHF patients.     

Role of vascular endothelial growth factor in angiodysplasia: an interventional study with thalidomide

Background and Aim: The pathogenesis of angiodysplasia is still not fully understood and effective therapy is not available. Thalidomide was reported to be effective in the treatment of angiodysplasia, but the mechanisms underlying its activity are, as yet, unknown. We aimed to investigate the expression of vascular endothelial growth factor (VEGF) in angiodysplasia tissues, and the role of hypoxia‐inducible factor‐1α (HIF‐1α) and basic fibroblast growth factor (bFGF) on VEGF expression in human umbilical vein endothelial cells (HUVEC). Additionally, we aimed to study the role of thalidomide in these parameters. Methods: Immunohistochemistry was performed to visualize VEGF in angiodysplasia lesions. HUVEC were incubated under hypoxic conditions or in the presence of bFGF. Effects of exposure to thalidomide were studied. Cell growth was assessed in methylthiazolyte‐trazolium assays. Enzyme‐linked immunosorbent assays and real‐time polymerase chain reaction were performed to assess the expression of VEGF at protein and mRNA levels. Western blot was performed to detect the expression of HIF‐1α under hypoxic conditions. Results: VEGF was strongly expressed in 75% of patients with angiodysplasia lesions, as compared to expression in patients without angiodysplasia lesions. VEGF was also induced in HUVEC under hypoxic conditions (P < 0.05). bFGF was found to stimulate the proliferation of HUVEC and enhance the expression of VEGF. Thalidomide suppressed bFGF‐induced proliferation significantly and decreased VEGF expression, both at the protein and mRNA levels. Thalidomide also inhibited HIF‐1α in a dose‐dependent manner (P < 0.05). Conclusions: VEGF may play an important role in the pathogenesis of angiodysplasia. Thalidomide can suppress VEGF, either induced by HIF‐1α or bFGF.     

Effect of interferon alpha and ribavirin treatment on serum levels of transforming growth factor-beta1, vascular endothelial growth factor, and basic fibroblast growth factor in patients with chronic hepatitis C

AIM: To assess the role of transforming growth factor-beta1 (TGF-beta1), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the pathogenesis of fibrosis associated with chronic hepatitis C (CHC) and to evaluate the influence of the antiviral therapy on above parameter levels depending on the treatment results (complete response or no response). METHODS: Study group included 100 patients with CHC, in whom fibrosis in liver specimens was assessed (Scheuer fibrosis score: 1-4 points). Control group included 30 subjects with antibodies anti-HCV present and persistently normal ALT level, without fibrosis (Scheuer fibrosis score: 0 points). Concentration of studied parameters was assayed in the serum by immunoenzymatic method before and after the therapy with interferon alpha-2b and ribavirin. RESULTS: TGF-beta1 levels were significantly higher in the study group compared to the control group (35.89 vs 32.37 ng/mL; P=0.023). Such differences were not found in VEGF and bFGF levels. In patients showing complete response (negative HCV RNA and normal ALT level), significant increase in VEGF (112.8 vs 315.03 pg/mL; P<0.05) and bFGF (2.51 vs 15.79 pg/mL; P=0.04) levels were found. Significant decrease in TGF-beta1 level was observed both in responders (37.44 vs 30.02 ng/mL; P=0.05), and in non-responders (38.22 vs 30.43 ng/mL; P=0.043). bFGF levels before the treatment were significantly lower (2.51 vs 5.94 pg/mL; P=0.04), and after the treatment significantly higher (15.79 vs 4.35 pg/mL; P=0.01) in patients with complete response than in those with no response. CONCLUSION: Among the analyzed parameters TGF-beta1 seems to play the most important role in the pathogenesis of fibrosis in CHC. Levels of this factor are significantly lower in subjects who do not have fibrosis developed in them. Good therapeutic effect in CHC patients is associated with significant changes in TGF-beta1, VEGF, and bFGF levels. bFGF seems to have the highest usefulness in the prognosis of treatment efficacy.     

Effect of statin therapy on dynamics of vascular endothelial growth factor and fibroblast growth factor in patients with ischemic heart disease

The aim of our study was to assess the influence of rosuvastatin on coronary angiogenesis. 30 male patients with chronic coronary heart disease and total cholesterol level > 5.2 mmol/l were treated with rosuvastatin 10 mg daily during 3 months. The serum level of total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides (TG) as well as C-reactive protein (CRP) and interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were measured initially and in 3 months. There was the significant decreasing of TC, LDL-C and TG concentrations. IL-6 and CRP serum levels were also decreased after rosuvastatin therapy. Three months of treatment resulted to significant decrease of VEGF with no changes of bFGF levels. The correlation was not found between CRP and VEGF levels and between IL-6 and VEGF levels. Also there was no correlation between the degree of decreasing CRP and VEGF, and IL-6 and VEGF. So we have shown significant decreasing of VEGF serum levels on rosuvastatin therapy. It could be possible mechanism of plaque stabilization in patients with coronary heart disease.