血管内皮生长因子对骨肉瘤的血管生成及转移预后的影响

背景血管内皮生长因子(VEGF)是肿瘤血管再生的重要刺激因子,肿瘤血管再生与众多肿瘤患者预后密切相关.骨肉瘤血管生成与预后的关系如何?目的研究VEGF对骨肉瘤血管生成、生长、转移及预后的影响.设计随机对照的实验研究.地点和对象实验地点唐都医院全军骨肿瘤研究所.对象69例骨肉瘤标本.干预对69例骨肉瘤患者的临床病理资料进行回顾性研究,应用CD34,VEGF单克隆抗体对其组织切片分别进行免疫组化染色,应用地高辛标记的VEGF探针对27例原发性骨肉瘤进行原位杂交染色.分析研究VEGF表达和CD34染色阳性血管密度与患者预后关系.主要观察指标血管内皮生长因子(VEGF)和微血管密度(MVD).结果VEGF阳性表达率为56.5%(39/69),VEGF阳性组肿瘤微血管计数(MVC)(35.7±9.8)及微血管周径(MVP)(2.76±0.18)μm明显高于VEGF阴性组[MVC(7.2±2.4)及MVP(0.62±0.04)μm].多元回归分析显示,血管密度增高及VEGF表达阳性与骨肉瘤患者的远隔转移发生、不良预后密切相关(P＜0.05).临床病理资料中,外科手术边界微小病灶阳性情况、Enneking外科分期、肿瘤大小和患者年龄与患者预后相关(P＜0.05).患者性别、手术方法分类以及病理亚型与预后无相关性.结论VEGF在骨肉瘤的血管生成和转移中起到重要作用,VEGF是骨肉瘤血管生成的决定性刺激因子,骨肉瘤MVD和骨肉瘤组织中VEGF表达情况是骨肉瘤患者的独立性预后因素.     

血管内皮生长因子表达与卵巢癌血管生成的关系

目的：探讨血管内皮生长因子（VEGF）的表达水平与卵巢癌血管生成的关系。方法：应用免疫组织化学染色技术分别检测37例卵巢癌组织（恶性组），30例良性卵巢肿瘤组织（良性组）和26例正常卵巢组织（正常组）中的微血管密度（MVD），同时测定卵巢癌组织中VEGF的表达水平。结果：恶性组的MVD值明显高于良性组，正常组（均为P＜0．01）。恶性组VEGF表达等级主要为高，中度表达；在良性组主要为中，低度表达；正常组中多数不表达。VEGF高度表达的卵巢癌组织中的MVD值显著高于VEGF代度表达者（P＜0．01），卵巢癌临床分期为晚期（Ⅲ，Ⅳ期），病理分级高（G2和G3）者与临床分期为早期（Ⅰ,Ⅱ期），病理分级低（G1）者比较，VEGF表达水平高。结论：卵巢癌组织的MVD值与病理分期，临床分级关系密切。VEGF表达水平高的卵巢癌组织的MVD值亦高，提示VEGF高表达可显著促进卵巢癌组织中的血管生成，与卵巢癌的浸润密切相关。     

真核表达载体血管内皮生长因子转染血管内皮细胞及对新生血管形成的影响

背景:血管内皮生长因子(vascular endothelial growth factor,VEGF)能与存在内皮细胞表面的特异性受体结合,刺激体内新生血管形成,但在体内半衰期极短,在移植局部难以维持足够的浓度,限制了其临床应用.目的:观察VEGF与增强绿色荧光蛋白(enhanced green fluorescent,EGFP)共表达载体转染对大鼠血管内皮细胞形成新生血管的影响.设计、时间及地点:随机分组设计、对照动物实验,于2004-09/2005-01在中国医科大学附属第一医院器官移植实验室完成.材料:30只雄性Wistar大鼠按随机数字表法分为3组,每组10只.质粒pIRES2-EGFP/VEGF165由第四军医大学提供.方法:采用层析法大量提取pIRES2-EGFPNEGF165质粒,采用阳性脂质体法进行转染,计数1×106血管内皮细胞植入雄性Wiser大鼠肾被膜下.实验组:植入转染质粒pIRES2-EGFP/VEGF165的内皮细胞:空白转染组:植入转染质粒pIRES2-EGFP的内皮细胞:对照组:植入正常大鼠血管内皮细胞.主要观察指标:①转染72 h后观察EGFP及VEGF表达情况.②流式细胞仪检测转染效率.③植入后14 d苏木精-伊红染色观察植入血管内皮细胞处组织形态学变化.结果:30只大鼠均进入结果分析.①荧光显微镜下实验组内皮细胞有特异性的EGFP表达.②流式细胞仪分析转染效率为13.06%.③实验组血管内皮细胞胞核和胞浆中均有VEGF表达.反转录-聚合酶链反应显示实验组大鼠血管内皮细胞中有人源化VEGF165基因在mRNA水平表达.④移植后14 d.实验组大鼠肾被膜下可见成团的新生毛细血管网形成,而对照组及空白转染组虽血管内皮细胞仍存活,但未形成明显血窦.结论:转染VEGF基因是促进内皮细胞早期(14d内)形成新生血管的有效途径.     

Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.

Vascular permeability factor (VPF) is an Mr 40-kD protein that has been purified from the conditioned medium of guinea pig line 10 tumor cells grown in vitro, and increases fluid permeability from blood vessels when injected intradermally. Addition of VPF to cultures of vascular endothelial cells in vitro unexpectedly stimulated cellular proliferation. VPF promoted the growth of new blood vessels when administered into healing rabbit bone grafts or rat corneas. The identity of the growth factor activity with VPF was established in four ways: (a) the molecular weight of the activity in preparative SDS-PAGE was the same as VPF (Mr approximately 40 kD); (b) multiple isoforms (pI greater than or equal to 8) for both VPF and the growth-promoting activity were observed; (c) a single, unique NH2-terminal amino acid sequence was obtained; (d) both growth factor and permeability-enhancing activities were immunoadsorbed using antipeptide IgG that recognized the amino terminus of VPF. Furthermore, 125I-VPF was shown to bind specifically and with high affinity to endothelial cells in vitro and could be chemically cross-linked to a high-molecular weight cell surface receptor, thus demonstrating a mechanism whereby VPF can interact directly with endothelial cells. Unlike other endothelial cell growth factors, VPF did not stimulate [3H]thymidine incorporation or promote growth of other cell types including mouse 3T3 fibroblasts or bovine smooth muscle cells. VPF, therefore, appears to be unique in its ability to specifically promote increased vascular permeability, endothelial cell growth, and angio-genesis.     

脑膜瘤血管内皮细胞生长因子的表达及血管生成与术后复发的关系

脑膜瘤是颅内常见肿瘤,手术切除效果较好,但其术后复发一直困扰着临床外科医师,即使手术达到S impson I级切除,术后仍有9%~15%的复发率[1]。近年研究发现血管内皮细胞生长因子(VEGF)与实体肿瘤的发生、生长、浸润和转移的关系密切[2],并已成为基础与临床研究的热点。(VEGF)是一     

Blockade of an angiotensin type I receptor enhances effects of radiation on tumor growth and tumor-associated angiogenesis by reducing vascular endothelial growth factor expression

Objective

Angiogenesis, the formation of new capillary blood vessels, is essential for tumor progression. We had reported that Type 1 angiotensin receptor (AT1-R) antagonist reduced tumor-associated angiogenesis. Since antiangiogenic agents were reported to enhance efficacy of radiation therapy, we tested here whether or not AT1-R blockade facilitates the effects of radiation.

Methods

1 × 10⁶ LLC cells were injected into the subcutaneous tissue of male C57BL/6 mice, and when the average tumor volume reached around 0.1 cm³, radiation doses (3, 5, 10, and 15 Gy) were given on day 1.

Results

The mean tumor volumes at day 22 were 6.39 (3 Gy), 6.15 (5 Gy), 5.15 (10 Gy), and 3.07 (15 Gy) cm³, respectively. Combination of 10 Gy radiation with AT1R antagonist TCV-116 (30 mg/kg) significantly inhibited tumor growth by 83% (1.47 ± 0.11 cm³, P < 0.01) in comparison with its inhibition of control tumors (8.81 ± 0.45 cm³). The same was true for mean vessel density, and the combination therapy markedly reduced tumor-associated angiogenesis. This was confirmed by the reduced expression of CD31. LLC tumor growth was blocked by neutralizing antibody against vascular endothelial growth factor (VEGF). Real-time PCR analysis of VEGF disclosed a marked reduction in the mice under combination therapy, compared with control mice.

Conclusions

These results suggest that combination of radiation with AT1-R blockade markedly reduced the LLC growth rate, and that this was due to reduction of neovascularization by reducing VEGF levels. Combination therapy consisting of radiation and AT1R blockade may become an effective novel strategy for cancer treatment.     

血管内皮生长因子治疗性血管生成作用与缺血性脑血管病

血管内皮生长因子是血管特异性生长因子,能特异性地作用于血管内皮细胞,诱导血管生成,在血管发生和血管形成过程中起重要作用.传统观念认为,成年脑部血管内皮细胞是不能增殖的,但近期的动物实验发现局灶性脑缺血后可诱导缺血半暗带区的新生血管形成.这种脑血管生成是通过血管生长因了与内皮细胞上表达的酪氨酸受体结合而调控的.但是这种血管形成数量有限,并不足以挽救血液灌注不足引起的损害.新近的研究已经证实,外源性给予血管牛长因子能刺激侧枝循环形成和增加局部血流,并且已在外周动脉闭塞性疾病和心肌缺血中成功应用,这种新的刺激和诱导新生血管形成新颖方法一治疗性血管生成,为治疗缺血件脑血管病提供了一条全新的思路.     

血管内皮生长因子及其受体在抗肿瘤血管生成中的研究进展

肿瘤生长和转移依赖于血管生成,肿瘤血管生成是一多因素、多步骤的复杂过程,受多种细胞因子、生长因子及其受体调控,其中血管内皮生长因子(VEGF)及其受体(VEGFR)被认为是最关键的调控因子,封闭VEGF功能和以VEGFR为靶点的抗肿瘤血管生成成为抗肿瘤的新策略。     

Comparison of vascular endothelial growth factor and basic fibroblast growth factor on angiogenesis in SCID mice.

Therapeutic angiogenesis is a promising approach to treat patients with cardiovascular disease, and will likely be critical to engineering large tissues. Many growth factors have been found to play significant roles in angiogenesis, and vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are the most extensively investigated angiogenic factors to date. However, the appropriate dose to obtain a desired response and the effectiveness of each factor, relative to the other, in promoting angiogenesis at a specific site in the body remains unclear. We have used alginate hydrogels as localized delivery vehicles for VEGF and bFGF, and compared the ability of these factors to promote new blood vessel formation in the subcutaneous tissue of severe combined immunodeficient (SCID) mice. We have found that the thickness of a granulation tissue layer formed around the gel and the number of blood vessels in the layer increased with the dose of VEGF in the gel, but the density of new blood vessels remained relatively constant. Sustained and localized delivery of bFGF from the gels, while similarly leading to an increase in the density of blood vessels in the granulation tissue, did not lead to as high of a blood vessel density as VEGF. The results of this study support previous studies demonstrating the utility of both VEGF and bFGF in promoting angiogenesis, and suggest VEGF is more appropriate for creating a dense bed of new blood vessels in this model.     

Parathyroid hormone stimulates the endothelial expression of vascular endothelial growth factor

Background We showed previously that parathyroid hormone (PTH) may stimulate the endothelial expression of pro‐atherosclerotic and pro‐inflammatory markers. Considering the impact of PTH on vasculature, we decided to evaluate its effect on mRNA and intra‐cellular protein expressions of endothelial vascular endothelial growth factor (VEGF) taking into account that VEGF may play a role in the pathogenesis of endothelial dysfunctions. Materials and methods Human umbilical vein cords endothelial cells (HUVEC) were stimulated for 24 h with 10^?12–10^?10 mol L^?1 PTH. The VEGF‐165 mRNA expression (critical in stimulating endothelial cell proliferation) was evaluated by RT/PCR and the intra‐cellular VEGF protein expression by flow cytometry. The pathways by which PTH may have an effect on VEGF expression were also evaluated. Results PTH (10^?10 mol L^?1) significantly increased VEGF‐165 mRNA expression (P < 0·05). The addition of 50 nmol L^?1 protein kinase C (PKC) and 10 µmol L^?1 protein kinase A (PKA) inhibitors significantly reduced the VEGF‐165 mRNA expression (P = 0·01). We also examined whether nitric oxide (NO) may be involved in the PTH‐induced stimulation of VEGF‐165 expression. Pre‐treatment of the cells with 200 µmol L‐nitro arginine methyl ester (L‐NAME, NO synthase inhibitor) was found to inhibit VEGF‐165 mRNA expression (P = 0·006). VEGF protein could not be detected in the medium of HUVEC but it was present in the cell cytoplasm. PTH had no significant effect on cytoplasmatic VEGF protein expression. Conclusion The stimulatory effect of PTH on endothelial VEGF‐165 mRNA expression is partly through PKC and PKA pathways and is also NO dependent.     

Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A) is a multifunctional cytokine with important roles in pathological angiogenesis. Using an adenoviral vector engineered to express murine VEGF-A(164), we previously investigated the steps and mechanisms by which this cytokine induced the formation of new blood vessels in adult immunodeficient mice and demonstrated that the newly formed blood vessels closely resembled those found in VEGF-A-expressing tumors. We now report that, in addition to inducing angiogenesis, VEGF-A(164) also induces a strong lymphangiogenic response. This finding was unanticipated because lymphangiogenesis has been thought to be mediated by other members of the VPF/VEGF family, namely, VEGF-C and VEGF-D. The new "giant" lymphatics generated by VEGF-A(164) were structurally and functionally abnormal: greatly enlarged with incompetent valves, sluggish flow, and delayed lymph clearance. They closely resembled the large lymphatics found in lymphangiomas/lymphatic malformations, perhaps implicating VEGF-A in the pathogenesis of these lesions. Whereas the angiogenic response was maintained only as long as VEGF-A was expressed, giant lymphatics, once formed, became VEGF-A independent and persisted indefinitely, long after VEGF-A expression ceased. These findings raise the possibility that similar, abnormal lymphatics develop in other pathologies in which VEGF-A is overexpressed, e.g., malignant tumors and chronic inflammation.     

钼靶X线征象与VEGF表达的相关性

目的 探讨钼靶X线征象与血管内皮生长因子(VEGF)表达的关系,并建立预测VEGF表达的回归方程,以期指导靶向药物贝伐单抗(AVASTIN)的使用.方法 回顾性分析144例浸润性乳腺癌患者的钼靶X线和病理检查资料,采用t检验和X2检验进行单因素分析,再行Logistic回归以发现独立的预测指标,建立回归方程;针对各预测指标进行受试者工作特征(ROC)曲线分析,判断回归方程的预测准确度.结果 单因素分析显示患者年龄、病理分级、肿块直径、肿块分叶征及毛刺征、淋巴结转移6个因素与VEGF蛋白的表达有显著相关性,但进入Logistic回归方程的变量为年龄、肿块直径及淋巴结转移,由回归方程产生各个体预概率P(PRE_1)的ROC曲线下面积为0.88,诊断价值较高.结论 年龄及钼靶X线表现中肿块直径和淋巴结转移对浸润性乳腺癌患者VEGF表达有较好的预测价值,可为临床使用AVASTIN提供指导.     

KRN633: A selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase that suppresses tumor angiogenesis and growth

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 play a central role in angiogenesis, which is necessary for solid tumors to expand and metastasize. Specific inhibitors of VEGFR-2 tyrosine kinase are therefore thought to be useful for treating cancer. We showed that the quinazoline urea derivative KRN633 inhibited tyrosine phosphorylation of VEGFR-2 (IC50 = 1.16 nmol/L) in human umbilical vein endothelial cells. Selectivity profiling with recombinant tyrosine kinases showed that KRN633 was highly selective for VEGFR-1, -2, and -3. KRN633 also blocked the activation of mitogen-activated protein kinases by VEGF, along with human umbilical vein endothelial cell proliferation and tube formation. The propagation of various cancer cell lines in vitro was not inhibited by KRN633. However, p.o. administration of KRN633 inhibited tumor growth in several in vivo tumor xenograft models with diverse tissue origins, including lung, colon, and prostate, in athymic mice and rats. KRN633 also caused the regression of some well-established tumors and those that had regrown after the cessation of treatment. In these models, the trough serum concentration of KRN633 had a more significant effect than the maximum serum concentration on antitumor activity. KRN633 was well tolerated and had no significant effects on body weight or the general health of the animals. Histologic analysis of tumor xenografts treated with KRN633 revealed a reduction in the number of endothelial cells in non-necrotic areas and a decrease in vascular permeability. These data suggest that KRN633 might be useful in the treatment of solid tumors and other diseases that depend on pathologic angiogenesis.     

卵巢肿瘤的血管内皮生长因子表达和肿瘤微血管密度计数的意义

目的探讨血管内皮生长因子(VEGF)蛋白表达和肿瘤微血管密度(MVD)与卵巢恶性肿瘤预后的关系。方法采用免疫组织化学染色的方法检测94例卵巢上皮性肿瘤患者(其中良性上皮性肿瘤患者17例,交界性上皮性肿瘤患者13例,上皮性卵巢癌患者64例)中VEGF表达情况及MVD计数。结果在上皮性卵巢癌、交界性上皮肿瘤、良性卵巢肿瘤中VEGF阴性分别为:2例(3%)、4例(31%)、16例(94%);VEGF低度表达分别为:31例(48%)、7例(54%)、1例(6%);VEGF高度表达分别为:31例(48%)、2例(15%)、0例。VEGF蛋白高度表达与肿瘤的临床分期、细胞分化程度及患者预后有明显的相关性。MVD与肿瘤的临床病理特征无明显的相关性。VEGF蛋白高度表达者的生存率比VEGF无或低度表达者差。结论VEGF蛋白表达的测定可以帮助判断卵巢上皮癌患者的预后,在指导临床治疗方面有重要意义。     

Spatiotemporal control of vascular endothelial growth factor delivery from injectable hydrogels enhances angiogenesis

Therapeutic angiogenesis with vascular endothelial growth factor (VEGF) delivery may provide a new approach for the treatment of ischemic diseases, but current strategies to deliver VEGF rely on either bolus delivery or systemic administration, resulting in limited clinical utility, because of the short half-life of VEGF in vivo and its resultant low and transient levels at sites of ischemia. We hypothesize that an injectable hydrogel system can be utilized to provide temporal control and appropriate spatial biodistribution of VEGF in ischemic hindlimbs. A sustained local delivery of relatively low amounts of bioactive VEGF (3 mug) with this system led to physiologic levels of bioactive VEGF in ischemic murine (ApoE(-/-)) hindlimbs for 15 days after injection of the gel, as contrasted with complete VEGF deprivation after 72 h with bolus injection. The gel delivery system resulted in significantly greater angiogenesis in these limbs as compared to bolus (266 vs. 161 blood vessels mm(-2)). Laser Doppler perfusion imaging showed return of tissue perfusion to normal levels by day 28 with the gel system, whereas normal levels of perfusion were never achieved with saline delivery of VEGF or in control mice. The system described in this article could represent an attractive new generation of therapeutic delivery vehicle for treatment of cardiovascular diseases, as it combines long-term in vivo therapeutic benefit (localized bioactive VEGF for 1-2 weeks) with minimally invasive delivery.     

肝细胞生长因子和血管内皮生长因子在急性髓系白血病中的表达以及与血管新生的关系

目的 探讨肝细胞生长因子(HGF)和血管内皮生长因子(VEGF)在急性髓系白血病(AML)中的表达及与AML血管新生的关系.方法 应用酶联免疫吸附试验(ELISA)测定AML 25例初发未治、17例完全缓解、16例未缓解、12例复发患者血清中HGF和VEGF的浓度,并与正常对照组比较.结果 血清HGF的浓度:AML初发未治组[(1357.29±358.64) ng/L]、未缓解组[(1175.93±306.71)ng/L]、复发组[(1261.21±340.83) ng/L]患者均明显高于正常对照组[(232.62±99.13) ng/L]和缓解组[ (256.65 ±94.32) ng/L](F=78.35,P＜0.01);血清VEGF的浓度:AML初发未治组[(253.84±49.14) ng/L]、未缓解组[(245.87±54.68) ng/L]、复发组[(264.75 ±62.52) ng/L]患者均明显高于正常对照组[ (97.61±16.19) ng/L]和缓解组[(99.76±15.93) ng/L](F=68.65,P＜0.01);缓解组患者血清HGF和VEGF的浓度与正常对照组比较,差异均无统计学意义(P均＞0.05).HGF和VEGF在AML中呈正相关(r=0.49,P＜0.05).结论 HGF和VEGF与AML的发生、发展密切相关,通过阻抗HGF治疗白血病有望成为新的治疗方法.     

血管内皮生长因子及其受体对类风湿关节炎新生血管的影响

目的:探讨血管内皮生长因子及其受体与类风湿关节炎新生血管的关系。资料来源:应用计算机检索Pubmed2000-01/2005-02有关血管内皮生长因子及其受体对类风湿关节炎血管新生的影响的文献,检索词“vascularendothelialgrowthfactor,vascularendothelialgrowthfactorreceptor,rheumatoidarthritis,angiogenesis”,并限定文章语言种类为English。资料选择:对检索到的血管内皮生长因子及其受体与类风湿关节炎血管新生方面的相关信息进行整理,选取针对性强的文章。同一领域的文献则选择近期发表或权威杂志的文章。资料提炼:共检索到37篇相关文献,其中19篇文章符合要求。排除18篇,其中15篇系重复同一研究,3篇为Meta分析。资料综合:血管内皮生长因子通过与其受体结合发挥生物学作用,促进内皮细胞有丝分裂,进一步增殖分化、迁移,导致血管新生,形成血管翳,在类风湿关节炎的病理过程中起关键作用。针对血管内皮生长因子从不同水平进行抗血管新生治疗类风湿关节炎取得了显著效果,为治疗类风湿关节炎提供了新的策略。结论:血管内皮生长因子在类风湿关节炎病理性新生血管化过程中所起的作用已基本肯定,但其作用途径尚未完全明确。抗血管新生从理论上为治愈类风湿关节炎提供了可能,但该类药物的安全性及更为精细的治疗靶点都有待于进一步探索。     

血管内皮生长因子及其受体对类风湿关节炎新生血管的影响

目的：探讨血管内皮生长因子及其受体与类风湿关节炎新生血管的关系.资料来源：应用计算机检索Pubmed 2000-01/2005-02有关血管内皮生长因子及其受体对类风湿关节炎血管新生的影响的文献,检索词＂vascular endothelial growth factor,vascular endothelial growth factor receptor,rheumatoid arthritis,angiogenesis＂,并限定文章语言种类为Ennlish.资料选择：对检索到的血管内皮生长因子及其受体与类风湿关节炎血管新生方面的相关信息进行整理,选取针对性强的文章.同一领域的文献则选择近期发表或权威杂志的文章.资料提炼：共检索到37篇相关文献,其中19篇文章符合要求.排除18篇,其中15篇系重复同一研究,3篇为Meta分析.资料综合：血管内皮生长因子通过与其受体结合发挥生物学作用,促进内皮细胞有丝分裂,进一步增殖分化、迁移,导致血管新生,形成血管翳,在类风湿关节炎的病理过程中起关键作用.针对血管内皮生长因子从不同水平进行抗血管新生治疗类风湿关节炎取得了显著效果,为治疗类风湿关节炎提供了新的策略.结论：血管内皮生长因子在类风湿关节炎病理性新生血管化过程中所起的作用已基本肯定,但其作用途径尚未完全明确.抗血管新生从理论上为治愈类风湿关节炎提供了可能,但该类药物的安全性及更为精细的治疗靶点都有待于进一步探索.     

Telmisartan-enhanced hypercholesterolaemic serum-induced vascular endothelial growth factor expression in immortalized human umbilical vascular endothelial cells

OBJECTIVE: To clarify whether hypercholesterolaemia can increase vascular endothelial growth factor (VEGF) expression in human umbilical vascular endothelial cells (HUVECs) through the phosphatidylinositol 3-kinase (PI3K) pathway, and whether a special angiotensin II receptor blocker, telmisartan, can attenuate VEGF expression induced by hypercholesterolaemia. METHODS: Levels of VEGF expression, PI3K activity and angiogenesis in vitro were determined by various methods after HUVECs were incubated with hypercholesterolaemic serum or combined with telmisartan and/or wortmannin. RESULTS: We found that hypercholesterolaemic serum (cholesterol > or = 0.08 mmol/L) can increase VEGF expression in HUVECs and that telmisartan cooperates with hypercholesterolaemic serum in promoting VEGF expression. The increased VEGF expression was associated with enhanced PI3K activity and could be significantly inhibited by wortmannin, a potent PI3K inhibitor. Likewise, hypercholesterolaemic serum significantly promoted angiogenesis in vitro, which could be inhibited when PI3K activity was suppressed. CONCLUSIONS: Our study suggests that hypercholesterolaemic serum induces VEGF expression through PI3K in HUVECs and that telmisartan cooperates with hypercholesterolaemia in promoting VEGF expression.