Immunohistochemical detection of vascular endothelial growth factor (VEGF) in the vasculature of oligodendrogliomas

C. Christov, H. Adle-Biassette, C. Le Guerinel, S. Natchev and R. K. Gherardi (1998) Neuropathology and Applied Neurobiology 24, 29–35 Immunohistochemical detection of vascular endothelial growth factor (VEGF) in the vasculature of oligodendrogliomas Vascular endothelial growth factor (VEGF) appears to be implicated in tumour angiogenesis. In the present study immunohistochemical expression of VEGF was evaluated in 34 oligodendrogliomas (13 grade II, 21 grade III [WHO]). VEGF immunoreactivity was found in 31 of 34 cases. Expression of VEGF was observed in endothelial cells and some vascular smooth muscle cells, but not in neoplastic oligodendrocytes. Vessel counts, percentages of VEGF-positive vessels and vessels with vascular endothelial proliferation were assessed. The degree of VEGF labelling and vascular-endothelial proliferation in each vessel were evaluated using a 3 degree intensity score. Expression of VEGF was higher in grade III than in grade II oligodendrogliomas as assessed by percentage of VEGF positive vessels (55.8 ± 29.2% vs 17.0 ± 19.0% [P < 0.001]) and by VEGF immunostaining intensity (1.90 ± 0.60 vs 0.90 ± 0.40 [P < 0.001]). VEGF expression did not correlate with vessel density. Intensity of VEGF expression correlated positively with that of vascular-endothelial proliferation in grade III tumours (r=+0.47 [P < 0.05]). The percentage of VEGF positive vessels showed some degree of positive correlation with the percentage of vessels showing vascular-endothelial proliferation (r=+408 [P < 0.10]). Within individual grade III tumours 67.5 ± 29.6% of all vessels with vascular-endothelial proliferation were VEGF-positive and 31.0 ± 20.5% of all VEGF-positive vessels showed no evidence of vascular-endothelial proliferation. We conclude that (i) expression of VEGF is observed in the vasculature of oligodendrogliomas; (ii) marked expression of VEGF is observed in grade III oligodendrogliomas; (iii) VEGF may be one of the interrelated causative stimuli acting in concert to induce vascular-endothelial proliferation.     

Enhancement of sciatic nerve regeneration after vascular endothelial growth factor (VEGF) gene therapy

F. R. Pereira Lopes, B. C. G. Lisboa, F. Frattini, F. M. Almeida, M. A. Tomaz, P. K. Matsumoto, F. Langone, S. Lora, P. A. Melo, R. Borojevic, S. W. Han and A. M. B. Martinez (2011) Neuropathology and Applied Neurobiology 37, 600–612 Enhancement of sciatic nerve regeneration after vascular endothelial growth factor (VEGF) gene therapy Aims: Recent studies have emphasized the beneficial effects of the vascular endothelial growth factor (VEGF) on neurone survival and Schwann cell proliferation. VEGF is a potent angiogenic factor, and angiogenesis has long been recognized as an important and necessary step during tissue repair. Here, we investigated the effects of VEGF on sciatic nerve regeneration. Methods: Using light and electron microscopy, we evaluated sciatic nerve regeneration after transection and VEGF gene therapy. We examined the survival of the neurones in the dorsal root ganglia and in lumbar 4 segment of spinal cord. We also evaluated the functional recovery using the sciatic functional index and gastrocnemius muscle weight. In addition, we evaluated the VEGF expression by immunohistochemistry. Results: Fluorescein isothiocyanate‐dextran (FITC‐dextran) fluorescence of nerves and muscles revealed intense staining in the VEGF‐treated group. Quantitative analysis showed that the numbers of myelinated fibres and blood vessels were significantly higher in VEGF‐treated animals. VEGF also increased the survival of neurone cell bodies in dorsal root ganglia and in spinal cord. The sciatic functional index and gastrocnemius muscle weight reached significantly higher values in VEGF‐treated animals. Conclusion: We demonstrate a positive relationship between increased vascularization and enhanced nerve regeneration, indicating that VEGF administration can support and enhance the growth of regenerating nerve fibres, probably through a combination of angiogenic, neurotrophic and neuroprotective effects.     

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) and its receptor flt-1 in microcystic meningiomas

We investigated the immunohistochemical expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) and of its endothelial cell receptor flt-1 in relationship to microcyst formation in meningiomas. Expression of VPF/VEGF was studied in 60 meningiomas (6 microcystic, 38 partially microcystic and 16 with no microcystic areas) and 30 meningiomas from these three subgroups were evaluated for flt-1 expression. VPF/VEGF immunoreactivity was mainly observed in vessel endothelium. Positive vessels were present in 75% (33/44) of meningiomas with any amount of microcystic pattern and in 38% (6/16) of the solid meningiomas (P < 0.02). Densities and percentages of both VPF/VEGF-positive and flt-1-positive vessels were higher in meningiomas with microcystic areas than in solid meningiomas (P≤ 0.002). The 6 microcystic meningiomas showed the highest densities and percentages of both VPF/VEGF-positive (P≤ 0.0002) and flt-1-positive vessels (P≤ 0.01). Vessel expression of VPF/VEGF and flt-1 were positively correlated (r≥ 0.75, P < 0.0001). A strong positive correlation between VPF/VEGF-positive vessel density and proportion of microcystic pattern in all 60 specimens was found (r = 0.75, P < 0.0001). We conclude that accumulation of flt-1-bound VPF/VEGF on endothelial cells of meningiomas is associated with microcyst formation that leads to the histologic appearance of microcystic meningiomas. Received: 18 January 1999 / Revised, accepted: 31 March 1999     

Expression of the axon‐guidance protein receptor Neuropilin 1 is increased in the spinal cord and decreased in muscle of a mouse model of amyotrophic lateral sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a degenerative motor neuron disorder. It is supposed that ALS is at least in part an axonopathy. Neuropilin 1 is an important receptor of the axon repellent Semaphorin 3A and a co‐receptor of vascular endothelial growth factor. It is probably involved in neuronal and axonal de‐/regeneration and might be of high relevance for ALS pathogenesis and/or disease progression. To elucidate whether the expression of either Neuropilin1 or Semaphorin3A is altered in ALS we investigated these proteins in human brain, spinal cord and muscle tissue of ALS‐patients and controls as well as transgenic SOD1^G93A and control mice. Neuropilin1 and Semaphorin3A gene and protein expression were assessed by quantitative real‐time PCR (qRT‐PCR), western blot and immunohistochemistry. Groups were compared using either Student t‐test or Mann–Whitney U test. We observed a consistent increase of Neuropilin1 expression in the spinal cord and decrease of Neuropilin1 and Semaphorin3A in muscle tissue of transgenic SOD1^G93A mice at the mRNA and protein level. Previous studies have shown that damage of neurons physiologically causes Neuropilin1 and Semaphorin3A increase in the central nervous system and decrease in the peripheral nervous system. Our results indicate that this also occurs in ALS. Pharmacological modulation of expression and function of axon repellents could be a promising future therapeutic option in ALS.     

EFFECTS OF VALSARTAN ON STRESS-INDUCED CHANGES OF SERUM VASCULAR ENDOTHELIAL GROWTH FACTOR AND NITRIC OXIDE IN MICE

This study investigated the effects of renin-angiotensin system (RAS) blockade on stress-induced changes of serum vascular endothelial growth factor (VEGF) and nitric oxide (NO) in mice. Chronic stress increased the serum NO levels significantly compared to control group (p = .0172). Valsartan, an angiotensin II receptor antagonist, alone, did not make significant difference versus control group. In chronic stress + valsartan group, serum NO levels decreased nonsignificantly compared to chronic stress group. There was a nonsignificant increase in serum VEGF levels after chronic stress. Valsartan alone or with chronic stress did not significantly affect the serum VEGF levels. In conclusion, there was no correlation between NO and VEGF changes during the stress response. In this respect, there may be other mechanisms to explain the stress-induced NO increase.     

慢性硬膜下血肿液中VEGF、D-二聚体的测定及意义

目的 探讨血肿液中血管内皮生长因子(VEGF)、D-二聚体的含量与慢性硬膜下血肿(CSDH)发生发展的关系.方法 利用酶联免疫吸附分析法(ELISA)及免疫散射比浊法对CSDH 患者血肿液和血清中VEGF、D-二聚体的含量进行测定.结果 血肿液中VEGF、D-二聚体的含量明显高于血清中的含量(P ＜0.001).结论 VEGF、D-二聚体在慢性硬膜下血肿的发病机制中起重要作用.     

Decreased serum angiogenin level in Alzheimer's disease

Background

It has been suggested that Alzheimer's disease (AD) is mediated by pathological angiogenesis. Vascular endothelial growth factor (VEGF), transforming growth factor β (TGF-β), and tumor necrosis factor α (TNF -α) may play important roles in inflammation and angiogenesis through effects on inflammatory cell infiltration or neovascularization in AD pathogenesis. A few studies on the roles of VEGF in AD have been reported recently. But, the results were inconsistent. Angiogenin, which is suspected to have a similar function as VEGF, however, has not yet been studied in patients with AD.

Objective

This study was performed to investigate the levels of angiogenin and vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptorI (VEGFR I), and vascular endothelial growth factor receptor II (VEGFR II) in serums of patients with AD, to compare their levels with control subjects, and to determine whether serum angiogenin, VEGF, VEGFR I, and VEGFR II levels are associated with Alzheimer's disease (AD).

Methods

Serum angiogenin, VEGF, VEGFR I, and VEGFR II levels were quantified at the time of diagnosis in 20 patients with definite AD, and 18 healthy controls, using a commercial ELISA kit.

Results

Patients with AD exhibited lower serum angiogenin (p = 0.003) and higher VEGF (p = 0.008) levels than control subjects. No difference in serum VEGFR I and VEGFR II concentrations was observed between AD patients and controls. There was a correlation between serum levels of angiogenin and cognitive function (MMSE-KC and CDR) in AD patients.

Conclusion

The increased serum level of VEGF and decreased serum angiogenin level were founded. Cognitive function was correlated with serum levels of angiogenin. Angiogenin may be involved in the pathogenesis of AD. Further study should be needed to evaluate the possibility of serum angiogenin as a biomarker of AD and as a predictor of disease progression.     

Immunohistochemical evaluation of the microvascular density through the expression of TGF‐β (CD 105/endoglin) and CD 34 receptors and expression of the vascular endothelial growth factor (VEGF) in oligodendrogliomas

Angiogenesis has been proposed as essential for the growth of solid tumors. The determinants of this process, the growth factors and the vascular endothelial receptors have brought a potential in the tumor prognostic determination as well as perspectives of “targets” for antiangiogenic therapy. In oligodendrogliomas (OL), angiogenesis is little known and/or has generated conflicting results. In order to clarify angiogenesis in OL, we have evaluated the immunohistochemical expression of vascular endothelial growth factor (VEGF) and the microvascular density (MVD) through the expression of TGF‐β (CD105/endoglin) (MVD‐CD105) and CD34 (MVD‐CD34) receptors using the Chalkley point method in 30 OL. No significant immune reaction was found for the VEGF. There was expression in <10% of tumor cells and/or staining of weak intensity in 15 (50.0%), >10% of cells and moderate intensity staining in 1 (3.33%), and negative expression in 14 (46.67%). If present, the expression was restricted to tumor and endothelial cells. Our findings suggest that VEGF has little influence on OL angiogenesis. All specimens showed CD105 and CD34 expression in the intratumor vascular endothelium, suggesting involvement of CD105 in OL angiogenesis. The mean ± SD MVD‐CD105 and MVD‐CD34 were 10.83 ± 2.24 and 11.00 ± 2.76 in OL (P = 0.086; r = 0.319); 10.00 ± 2.00 and 10.40 ± 3.02 in OL grade II (n = 15) (P = 0.547; r = 0.105), and 11.67 ± 2.22 and 11.53 ± 2.45 in OL grade III (n = 15) (P = 0.817; r = 0.551), respectively. The absence of correlation between DMV‐CD105, DMV‐CD34 and tumor grades suggests that anti‐CD105 and anti‐CD34 antibodies have different vascular specificities. MVD‐CD105 was greater in OL grade III than in OL grade II (P = 0.0032), indicating an increase in the vascular neoformation, something which must be evaluated as a possible prognostic factor in OL. Both TGF‐β and CD105 bring perspectives as “targets” for antiangiogenic treatments in OL.     

Regression of retinal capillaries following N‐methyl‐D‐aspartate‐induced neurotoxicity in the neonatal rat retina

Degeneration of retinal capillaries occurs following N‐methyl‐D ‐aspartate (NMDA)‐induced retinal neurotoxicity, and the degree of capillary degeneration decreases in an age‐dependent manner. To determine the role of vascular endothelial growth factor (VEGF) in the high susceptibility of capillaries to neuronal damage during the early postnatal stage, this study compares the vascular regression patterns between NMDA‐treated retinas and retinas treated with N‐[2‐chloro‐4‐{(6,7‐dimethoxy‐4‐quinazolinyl)oxy}phenyl]‐N′‐propylurea (KRN633), a VEGF receptor tyrosine kinase inhibitor, in neonatal rats. Two days after a single intravitreal injection of NMDA (200 nmol/eye) on postnatal day (P) 7, substantial retinal neuron loss and delayed expansion of the retinal vascular bed were observed. The reduction in the capillary density in the central retina reached statistical significance 4 days after NMDA treatment. In retinas of rats injected subcutaneously with KRN633 (10 mg/kg) on P7 and P8, simplified vasculature attributable to capillary regression and prevention of endothelial cell growth were seen on P9, whereas no visible changes in the morphology of the retinal layers were observed. The degree of capillary degeneration in NMDA‐treated retinas was less than that in KRN633‐treated retinas. No apparent changes in immunoreactivities for VEGF were found 2 days after NMDA treatment. These results indicate that neuronal cell loss in the retina precedes retinal capillary degeneration following NMDA treatment, and VEGF‐dependent immature capillaries might be more susceptible to NMDA‐induced neuronal damage. © 2014 Wiley Periodicals, Inc.     

Low serum VEGF levels are associated with Alzheimer's disease

OBJECTIVE: As vascular endothelial growth factor (VEGF) determines important neurotrophic and neuroprotective actions, we postulated serum VEGF levels could be abnormally low in patients with Alzheimer's disease (AD). METHODS: We measured serum VEGF levels (VEGF(165) isoform by ELISA) in 51 patients with AD by National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorder Association criteria and compared with 66 age- and gender-matched non-demented controls. Patients with AD were stratified into levels of dementia severity by the Clinical Dementia Rating scale. Serum VEGF levels were stratified into upper (>309 pg/ml), middle (207-309 pg/ml), and lower (<207 pg/ml) tertiles. VEGF (-2,578) (rs 699,947) and VEGF (-634) (rs 2,010,963) polymorphisms were genotyped in patients with AD and controls. RESULTS: The mean concentration of VEGF in the serum of patients with AD (215.9 pg/ml, SD 101.5) was significantly lower than that of the controls (308.6 pg/ml, SD 223.9, P = 0.004), and decreased serum VEGF levels were associated with AD in a dose-dependent manner, the lower tertile of serum VEGF levels being associated with a fivefold increased risk for AD when compared with the upper tertile. There was no significant correlation between serum VEGF levels and age, sex, APOE alleles, AD dementia severity nor VEGF gene polymorphisms. CONCLUSION: Decrease in serum VEGF levels could contribute to the neurodegenerative process in AD.     

Elevated serum vascular endothelial growth factor in treatment-resistant schizophrenia treated with electroconvulsive therapy: Positive association with therapeutic effects

Objectives: As the name implies, vascular endothelial growth factor (VEGF) enhances angiogenesis, promotes vascular permeability, and stimulates neurogenesis in the adult brain. Furthermore, animal model studies have shown that electroconvulsive therapy (ECT), which is primarily utilised in cases of treatment-resistant schizophrenia (TRS), regulates the expression of VEGF. The current study focuses largely on the effect of ECT on VEGF serum concentration, and the relationship between VEGF and therapeutic effects in patients diagnosed with TRS.

Methods: Participants comprised 40 TRS patients and 43 healthy controls. Clinical severity was assessed (i.e. 1?day before commencement of ECT and 1?day following ECT) using the positive and negative syndrome scale (PANSS). Blood samples were also collected for VEGF measurements at corresponding time points.

Results: Pre-treatment serum VEGF levels were significantly lower in TRS patients compared to healthy controls. VEGF concentrations increased significantly following ECT, whereas no difference was found in controls. Moreover, there was a positive correlation between the change in VEGF and therapeutic effects.

Conclusions: Elevated serum VEGF in TRS treated with ECT is positively associated with therapeutic effects, suggesting that alterations in VEGF levels may constitute an index by which to evaluate the improvement in clinical condition.     

老年血管性痴呆患者血清HIF-1α、VEGF的变化及相关性研究

目的研究老年人血管性痴呆(Va D)患者血清低氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)水平的变化。方法检测88例老年Va D患者和30例健康老年人血清HIF-1α、VEGF水平的含量,比较两组间血清HIF-1α、VEGF水平的差异;分析血清HIF-1α、VEGF水平与痴呆程度的关系。结果老年人Va D患者血清HIF-1α、VEGF水平较正常健康老年人明显增高(P0.01)。不同痴呆程度的老年Va D患者血清HIF-1α、VEGF水平的比较差异没有统计学意义(P0.05)。结论血清HIF-1α、VEGF水平与老年人Va D有密切相关。     

Overproduction of vascular endothelial growth factor/vascular permeability factor is causative in crow–fukase (POEMS) syndrome

Crow–Fukase or POEMS syndrome of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes is a rare multisystem disorder of obscure pathogenesis that is associated with microangiopathy, neovascularization, and accelerated vasopermeability. We examined the levels of the vascular endothelial growth factor/vascular permeability factor (VEGF) in the serum and cerebrospinal fluid (CSF) from 10 patients with this syndrome. Serum VEGF levels were about 15–30 times those in control subjects or patients with Guillain–Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and other neurological disorders. The CSF VEGF levels, however, were similar to those found in GBS and CIDP. Elevated VEGF levels in the serum decreased in 7 patients with Crow–Fukase syndrome after conventional therapy. The principal isoform of VEGF in Crow–Fukase syndrome was VEGF165. Elevated VEGF was independent of M-protein. Our results suggest that the overproduction of VEGF is important in the pathogenesis of this disorder. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1390–1397, 1998     

Serum VEGF levels in acute ischaemic strokes are correlated with long-term prognosis

Background and purpose:  We investigated whether serum vascular endothelial growth factor (VEGF) levels in acute-stage ischaemic stroke patients with small vessel disease (SVD) or large vessel disease (LVD) are correlated with long-term prognoses, based on the difference in NIH Stroke Scale (NIHSS) scores between acute and chronic stages.
Methods:  From March 2007 to May 2008, we evaluated patients who experienced an ischaemic stroke for the first time, defined as SVD ( n  = 89) or LVD ( n  = 91) using the TOAST classification. Serum samples were taken immediately after admission (within 24 h of stroke onset) to evaluate VEGF levels. After 3 months, follow-up NIHSS scores were collected for all patients.
Results:  Serum VEGF levels in the acute stage (within 24 h of stroke onset) were higher in the LVD group than in the SVD group and were correlated with infarction volume. The increase in serum VEGF levels in the acute stage was proportional to an improved NIHSS score after 3 months. After adjustment for covariates, serum VEGF levels in the acute stage were still significantly correlated with the long-term prognosis of ischaemic stroke.
Conclusion:  Serum VEGF levels are correlated with long-term prognoses in acute ischaemic stroke patients.     

Vascular endothelial growth factor prolongs survival in a transgenic mouse model of ALS

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with the death of motor neurons in the spinal cord and brainstem. The cause of ALS is unknown and there is no cure. This study demonstrates, for the first time, that vascular endothelial growth factor (VEGF) delays progression of symptoms and prolongs survival in a Cu/Zn superoxide dismutase (SOD1) transgenic mouse model of ALS. These observations suggest that VEGF or related compounds, might be of value in the treatment of ALS patients.     

局灶性脑缺血大鼠血管内皮生长因子的表达及意义

目的 :研究大鼠局灶性脑缺血后血管内皮细胞生长因子 (VEGF)表达的动态变化。方法 :采用尼龙线栓法制作大鼠局灶性永久性大脑中动脉闭塞模型 ,用免疫组织化学方法观察大鼠缺血后 3、6、12h和 1、2、3、7d时 ,VEGF表达的情况。结果 :大鼠缺血后 3h ,缺血侧脑组织开始出现VEGF表达 ,2 4h明显增多 ,2d达高峰 ,7d时仍有少量表达。各时间占VEGF的表达主要集中在梗死灶周围。结论 :VEGF可能参与缺血性脑损伤的病理发展及修复过程     

Cerebrospinal fluid vascular endothelial growth factor in patients with amyotrophic lateral sclerosis

Oxidative stress and glutamate-mediated toxicity may play an important role in the etiopathogenesis of amyotrophic lateral sclerosis (ALS). The vascular endothelial growth factor (VEGF) is a neuroprotective cytokine activated by hypoxia. The aim of this study was to measure VEGF levels in the cerebrospinal fluid (CSF) of ALS patients. The study concerned 30 ALS patients and 30 control subjects. The VEGF was measured by the enzyme-linked immunosorbent assay. The results have shown that CSF VEGF levels are significantly increased in patients with long duration of ALS and in patients with limb-onset of the disease compared with controls (P<0.05). Moreover, the type of ALS patients’ subgroup significantly influences CSF VEGF levels (P=0.05). The CSF VEGF levels were significantly increased in patients with limb-onset compared to patients with bulbar-onset of ALS, and in patients with long duration of ALS compared to patients with its short duration (P<0.05). There was a significant correlation between CSF VEGF levels and duration of ALS (P<0.05). It seems that a significant increase in CSF VEGF levels in patients with limb-onset of ALS and in patients with long duration of the disease may have a protective role against glutamate-mediated toxicity and oxidative damage of motor neurons. However, the conclusions are limited due to relatively small subgroups of ALS patients and by lack of a control group consisting of healthy persons. Further investigations could help to confirm the results from this preliminary report.     

Altered serum levels of vascular endothelial growth factor and glial-derived neurotrophic factor but not fibroblast growth factor-2 in treatment-naive children with attention deficit/hyperactivity disorder

Abstract

Background and aim: Recent evidence suggests that growth factors might be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The aim of this study was to determine whether serum levels of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3), nerve growth factor (NGF), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) were altered in children with ADHD.

Methods: Serum levels of BDNF, GDNF, NT-3, NGF, VEGF and FGF-2 were analyzed in 49 treatment- naive children with ADHD and age, gender matched 36 healthy controls using enzyme-linked immunosorbent assay. ADHD symptoms were scored by Du Paul ADHD Rating Scale and Strengths and Difficulties Questionnaire.

Results: We found that serum VEGF levels were significantly lower (p?<?0.001) and GDNF levels were significantly higher in ADHD group compared to control group (p?=?0.003). However, we found no correlations between ADHD symptoms and serum VEGF or GDNF levels. Furthermore, we observed no significant alterations in serum BDNF, NT-3, NGF, FGF-2 levels in children with ADHD.

Conclusion: To our knowledge, the present study is the first to examine serum VEGF and FGF-2 levels in children with ADHD. Our results indicate that VEGF and GDNF might be involved in the etiology of ADHD. Further studies are required to determine the role of growth factors in the etiology and consequently in the treatment of ADHD.     

纤维蛋白对大鼠脑血管内皮细胞血管内皮生长因子表达的影响

目的观察纤维蛋白对大鼠脑血管内皮细胞血管内皮生长因子(VEGF)转录及蛋白水平表达的影响。方法大鼠脑血管内皮细胞分离后培养,加入不同浓度的纤维蛋白,通过Real-time PCR检测VEGF转录水平,应用酶联免疫方法(ELISA)定量检测培养基和细胞裂解液中的VEGF水平。结果纤维蛋白可以特异性诱导大鼠脑血管内皮细胞表达VEGF;加入不同浓度的纤维蛋白(0.03mg/ml、0.1mg/ml、0.3mg/ml和1.0mg/ml),24h后,1.0mg/ml纤维蛋白组的培养基VEGF水平显著增高(P<0.001);1.0mg/ml纤维蛋白与大鼠脑血管内皮细胞分别培养0、2、4、8、24、48h,VEGF浓度在共培养2h已经升高,8h时显著升高,在24h时仍然保持在显著升高表达水平(P<0.005),48h有所下降;Real-time PCR结果提示,大鼠脑血管内皮细胞中VEGF mRNA的上调呈现出剂量和时间依赖性增加。结论纤维蛋白可以上调大鼠血管内皮细胞中的VEGF。     

血管内皮生长因子与周围神经病变

简介VEGF及其受体的结构和功能,复习VEGF在糖尿病引起的外周神经病变以及其他类型神经病变的发生过程中所起的作用。研究显示转基因或其他干VEGF的措施,可能成为将来治疗一些神经病变的有效措施之一。