Vascular Endothelial Growth Factor Levels In Patients Research Articles

Reductions of Circulating Matrix Metalloproteinase 2 and Vascular Endothelial Growth Factor Levels after Treatment with Pegvisomant in Subjects with Acromegaly

Vascular endothelial growth factor (VEGF) is involved in activation of the matrix metalloproteinase (MMP) system; the latter is implicated in atherosclerosis and cardiovascular disease. Patients with acromegaly have reduced life expectancy primarily due to cardiac disease. This study assessed plasma MMPs and VEGF levels in patients with active acromegaly (IGF-I > 130% upper limit of normal), and on treatment with pegvisomant. Twenty patients [nine female, mean age 56.1 +/- 13.8 yr (mean +/- sd)] were studied at baseline and on pegvisomant therapy and compared with data from 25 healthy volunteers (12 female; 56.6 +/- 14.2 yr). Plasma MMP-2, MMP-9, and VEGF levels were measured. Serum IGF-I fell from a baseline (mean +/- sd) level of 620.1 +/- 209.3 ng/ml to 237.5 +/- 118.5 ng/ml on pegvisomant (doses 10-60 mg; P < 0.001). MMP-2 levels at baseline were significantly higher in patients compared with healthy controls (380.7 +/- 204.8 vs. 207.4 +/- 62.6 ng/ml; P < 0.001), but with treatment a significant reduction in MMP-2 [380.7 +/- 204.8 vs. 203.0 +/- 77.4 ng/ml; P < 0.001] and VEGF (283.4 +/- 233.6 vs. 229.1 +/- 157.4 pg/ml; P = 0.008) was noted. There was no significant difference in MMP-9 levels between patients and controls at baseline (797.5 +/- 142.1 vs. 788.3 +/- 218.0 ng/ml; P = 0.87) or between baseline and posttreatment levels (797.5 +/- 142.1 vs. 780.0 +/- 214 ng/ml; P = 0.76). Our novel data demonstrate that treatment of acromegaly with pegvisomant leads to reductions in MMP-2 and VEGF concentrations. Further studies are required to determine the significance of these findings with relation to cardiac disease.

Vascular endothelial growth factor levels in post-CABG pleural effusions are associated with pleural inflammation and permeability

Vascular endothelial growth factor (VEGF) participates in the pathogenesis of exudative pleural effusions (PEs). In the present study, we determined the pleural fluid (PF) and serum VEGF levels in patients with post-coronary artery by-pass grafting (post-CABG) PEs. Thirty-eight patients with post-CABG (two with bilateral) PEs were studied. PEs were divided into "early" (occurring earlier than 30 days after surgery) and "late" ones. VEGF levels were measured using ELISA. (i) Serum and PF VEGF levels did not differ significantly when all the patients (P=0.053) or those with late effusions (P=0.6) were analyzed; serum VEGF levels were significantly elevated in comparison to PF VEGF levels in patients with early (P=0.007) effusions. (ii) Serum VEGF levels were significantly higher in patients with early than in those with late effusions (P=0.033), while PF VEGF levels were not significantly different between the two groups (P=0.77). (iii) PF VEGF levels were higher than corresponding serum levels in 4/24 patients with early and in 10/16 patients with late post-CABG PEs (P=0.006). (iv) In PEs VEGF levels significantly correlated with red blood cells (P=0.015), nucleated cells (P=0.003), protein levels (P=0.002) and lactate dehydrogenase (LDH) levels (P=0.04). In post-CABG PEs, preferential local production of VEGF in the pleural cavity is most commonly observed a month or later after surgery. The fact that in PEs VEGF levels correlate with markers of pleural inflammation (inflammatory cells and LDH levels) and vascular hyperpermeability (protein levels) suggests that VEGF may be involved in the pathogenesis of post-CABG PEs.

Angiopoietin-2 Levels Are Elevated in Exudative Pleural Effusions

To examine the pleural fluid (PF) and serum levels of angiopoietin (Ang)-1, Ang-2, and vascular endothelial growth factor (VEGF) in patients with pleural effusions (PEs). One hundred fifteen patients, 16 with transudative PEs due to heart failure and 99 with exudative PEs (malignant, 40; para-pneumonic, 24; tuberculous, 13; miscellaneous etiologies, 22) were included in the study. PF and serum levels of the growth factors were measured using enzyme-linked immunosorbent assay. PF Ang-2 and VEGF levels but not Ang-1 levels were higher (p < 0.001) in exudates than in transudates. PF Ang-2 levels were higher in tuberculous PEs than in PEs of any other etiology and were lower in heart failure PEs than in PEs of any other etiology. The highest PF VEGF levels were observed in patients with malignant and parapneumonic PEs. The lowest PF VEGF levels were observed in patients with transudates. In PEs, Ang-2 levels correlate with VEGF levels (p < 0.001), RBC count (p = 0.002), nucleated cell count (p < 0.001), total protein levels (p < 0.001), and lactate dehydrogenase levels (p < 0.001). PF Ang-1 levels were lower than serum Ang-1 levels both in patients with exudates (p < 0.001) and in those with transudates (p = 0.001). PF Ang-2 levels were higher than serum Ang-2 levels both in patients with exudates (p < 0.001) and in those with transudates (p = 0.045). PF VEGF levels were higher than serum VEGF levels in patients with malignant PEs (p < 0.001) and parapneumonic PEs (p = 0.003), but lower than serum VEGF levels in heart failure PEs (p < 0.001). In patients with tuberculous PEs and exudative PEs of miscellaneous etiology, PF and serum VEGF levels did not differ significantly. Ang-2 levels but not Ang-1 levels are elevated in exudative PEs, and they correlate with levels of VEGF and markers of pleural inflammation. It is thus possible that Ang-2 along with VEGF participate in pleural inflammation and the pathogenesis of exudative PEs.

Effect of paclitaxel on vascular endothelial growth factor (VEGF) and interleukin (IL)-8 in serum of patients with recurrent ovarian cancer: a comparison of weekly vs triweekly regimens

Antiangiogenic scheduling of cancer chemotherapeutics has been increasingly recognized to be a potential application of the paclitaxel in cancer therapy. The purpose of this study is to confirm antiangiogenic effects of weekly low-dose paclitaxel in recurrent ovarian carcinoma. Measurements of serum vascular endothelial cell growth factor (VEGF) and interleukin (IL)-8 were performed using enzyme-linked immunosorbent assay (ELISA) kits. Serum was collected with written informed consents. Serum levels of VEGF and IL-8 were measured in patients with benign ovarian tumors, low malignant potential ovarian tumors (LMP), and ovarian carcinomas. Among 20 patients with pretreated recurrent ovarian carcinoma, 10 patients receiving treatment with paclitaxel (180 mg/m2) given once every 3 weeks (triweekly paclitaxel) and the other 10 patients receiving treatment with weekly paclitaxel (80 mg/m2) were randomly allocated. Sera from these patients were collected before treatment and 3 weeks after initiation of treatment to determine changes of VEGF and IL-8 levels. Although VEGF levels were highest in patients with ovarian carcinoma, there was no significant difference among benign, LMP, and carcinoma. Among patients with detectable levels of IL-8, ovarian carcinoma showed significantly higher IL-8 levels than benign tumors followed by LMP. VEGF levels in patients with treatment by triweekly paclitaxel did not show any significant change before and after treatment, while those in patients with treatment by weekly paclitaxel decreased significantly after treatment. Similarly, in patients with detectable IL-8 levels, weekly paclitaxel resulted in a significant decrease of IL-8 levels after treatment, while triweekly paclitaxel did not result in any significant change of IL-8 levels. The present study demonstrated that weekly but not triweekly paclitaxel had significant antiangiogenic effects.

The significance of vascular endothelial growth factor(VEGF) in children with asthma and pneumonia

Purpose:Vascular endothelial growth factor(VEGF) is a key cytokine for controlling vascular permeability and angiogenesis, which is one of the major findings in airway remodeling. However, it is not well known if it is associated with acute lower respiratory tract disease such as lobar pneumonia. The aim of this study is to compare serum VEGF levels in patients with asthma according to its severity and duration of cough, and to compare its levels with children with lobar pneumonia. Methods:Using a sandwich enzyme-linked immunosorbent assay, the serum VEGF levels were measured in 16 mild asthmatics, 14 moderate to severe asthmatics, six children with lobar pneumonia, and 22 control subjects. The asthmatics were also classified into three groups according to the duration of cough. Serum VEGF levels were compared in each group. Results:Serum VEGF levels were significantly increased in the children with moderate to severe asthma and lobar pneumonia compared to the children with mild asthma and control subjects. Serum VEGF levels were higher in children with chronic coughs of more than two weeks than in children with coughs lasting less than two weeks. Serum levels of VEGF showed positive correlations with blood platelet and white blood cell counts. Conclusion:VEGF increased according to the severity of asthma and duration of cough in children with asthma. It may play an important role not only in chronic airway inflammation, but also in the acute inflammation in children with lower respiratory tract disease

Clinical significance of measurement of plasma vascular endothelial growth factor(VEGF) levels in patietns with type 2 diabetes

目的 探讨糖尿病肾病(DN)患者血管内皮生长因子(VEGF)水平变化.方法用酶联免疫法测定60例糖尿病肾病组(DN组)、65例糖尿病非肾病组(NDN组)患者和40例正常对照组血浆中血VEGF、糖化血红蛋白(HbA1c)及尿微量白蛋白(UmALB)的水平.结果 DN组和NDN组患者VEGF、HbA1c及UmALB水平均明显高于正常对照组(P＜0.01);DN组VEGF、HbA1c及UmALB明显高于NDN组(P＜0.01);两组糖尿病患者血浆VEGF与HbA1c、UmALB水平呈显著正相关(P＜0.05).结论糖尿病患者血浆VEGF明显升高,可能参与DN的发生和发展过程。

Erythropoietin as a Retinal Angiogenic Factor in Proliferative Diabetic Retinopathy

Although vascular endothelial growth factor (VEGF) is a primary mediator of retinal angiogenesis, VEGF inhibition alone is insufficient to prevent retinal neovascularization. Hence, it is postulated that there are other potent ischemia-induced angiogenic factors. Erythropoietin possesses angiogenic activity, but its potential role in ocular angiogenesis is not established. We measured both erythropoietin and VEGF levels in the vitreous fluid of 144 patients with the use of radioimmunoassay and enzyme-linked immunosorbent assay. Vitreous proliferative potential was measured according to the growth of retinal endothelial cells in vitro and with soluble erythropoietin receptor. In addition, a murine model of ischemia-induced retinal neovascularization was used to evaluate erythropoietin expression and regulation in vivo. The median vitreous erythropoietin level in 73 patients with proliferative diabetic retinopathy was significantly higher than that in 71 patients without diabetes (464.0 vs. 36.5 mIU per milliliter, P<0.001). The median VEGF level in patients with retinopathy was also significantly higher than that in patients without diabetes (345.0 vs. 3.9 pg per milliliter, P<0.001). Multivariate logistic-regression analyses indicated that erythropoietin and VEGF were independently associated with proliferative diabetic retinopathy and that erythropoietin was more strongly associated with the presence of proliferative diabetic retinopathy than was VEGF. Erythropoietin and VEGF gene-expression levels are up-regulated in the murine ischemic retina, and the blockade of erythropoietin inhibits retinal neovascularization in vivo and endothelial-cell proliferation in the vitreous of patients with diabetic retinopathy in vitro. Our data suggest that erythropoietin is a potent ischemia-induced angiogenic factor that acts independently of VEGF during retinal angiogenesis in proliferative diabetic retinopathy.

Significance of serum vascular endothelial growth factor test before radiotherapy in patients with nasopharyngeal carcinoma

To study the changes of serum vascular endothelial growth factor (VEGF) and beta 2-microglobulin levels before and after radiotherapy in 58 patients with nasopharyngeal carcinoma (NPC), and to elucidate the clinical significance of VEGF and beta 2-microglobulin test before radiotherapy. Serum VEGF level was measured by sandwich ELISA in 58 patients with NPC and 24 healthy individuals, and the serum beta 2-microglobulin was assayed with time-resolved fluoroimmunoassay. The serum VEGF level in patients with NPC was (174.0+/-130.0) ng/L, higher than (134.1+/-66.6) ng/L of the healthy subjects, but the difference was not significant (P>0.05). The serum VEGF level was higher in T4 and IV a patients with NPC. No significant differences in the levels of serum VEGF were found among various N classifications in the patients with NPC. Patients with the serum VEGF level higher than 267.3 ng/L (mean+2 s of the serum VEGF level in the healthy individuals) had a shorter metastasis-free survival time (P<0.05). Although the patients with high beta 2-microglobulin level had a shorter survival time, the difference was not significant. The NPC patients with high serum VEGF level have a poor prognosis.

Angiogenic cytokines in serum and cutaneous lesions of patients with polyarteritis nodosa

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are angiogenic cytokines, that have been reported to elevate serum levels in patients with collagen diseases such as systemic sclerosis and dermatomyositis as well as in those with inflammatory bowel diseases. In this study, the serum levels of bFGF and VEGF were measured by using enzyme-linked immunosorbent assay in 20 patients with polyarteritis nodosa (PAN; 5 with systemic PAN and 15 with cutaneous PAN) and in 20 control subjects. We also investigated the expression of bFGF and VEGF in cutaneous lesions of patients by using immunohistochemical methods. Basic FGF was undetectable in the serum of control subjects, but detectable levels were found in 4 of 5 patients with classical PAN and 3 of 15 patients with cutaneous PAN. The serum bFGF level in these patients with systemic PAN was significantly elevated in comparison with that in healthy control subjects. The VEGF level was 178 +/- 41 pg/mL in the serum of healthy individuals. The mean VEGF level in patients with systemic or cutaneous PAN was significantly higher than that in healthy controls. Serum bFGF and VEGF levels in patients with systemic PAN were significantly elevated in comparison with those having cutaneous PAN. Immunohistochemical studies showed elevated bFGF expression on damaged endothelial cells in necrotizing vasculitis lesions. Elevated expression of bFGF was also observed on fibroblasts around the vasculitis. Some of the infiltrating cells around vasculitis lesions expressed VEGF. The study was small. Serum bFGF and VEGF levels may be useful markers of the disease activities of PAN.

Vascular endothelial growth factor (VEGF) levels and mutation of the BRCA1 gene in breast cancer patients

The aim of the study was to compare VEGF serum levels in breast cancer patients with and without BRCA1 gene mutation. We enrolled 80 patients, 22 premenopausal and 58 postmenopausal. We found statistically significant lower levels of VEGF in patients with BRCA1 gene mutation as compared with breast cancer patients without this mutation.

Elevated levels of plasma VEGF in patients with dengue hemorrhagic fever

Vascular endothelial growth factor (VEGF) can be produced by monocytes and endothelial cells. It plays important role in angiogenesis and vascular permeability. The phenomenon of extensive plasma leakage into various serous cavities of the body is a cardinal symptom of dengue hemorrhagic fever (DHF). This study was performed to investigate the role of VEGF in patients with DHF. Plasma samples collected from the 53 dengue fever (DF) patients (including 14 patients with DHF), and 5 additional subjects with non-dengue febrile illness as controls were tested for VEGF levels using commercial enzyme-linked immunosorbent assay (ELISA) kits. The results showed that median plasma levels of VEGF in the patients with DHF (54.6 pg ml −1) were significantly higher than those of DF (14.6 pg ml −1) and control group (27.1 pg ml −1) ( P < 0.05). In addition, VEGF levels in DF patients were not significantly different from those of control patients with non-dengue febrile illness ( P = 0.17). Multiple regression analysis was used to analyze the clinical variables independently associated with VEGF levels. The data showed that D-dimer levels were significantly associated with VEGF levels. In this study, plasma VEGF levels in patients with DHF were significantly higher than values from DF patients. The association between increased plasma VEGF levels and increased plasma D-dimer levels in the patients with dengue illness suggests that activation of the fibrinolytic system may play a role in VEGF production in the patients with DF.

Vascular endothelial growth factor (VEGF), prostaglandin E2 (PGE2) and active renin in hypertension of adrenal origin

There are limited data regarding the role of vascular endothelial growth factor (VEGF) in arterial hypertension. The aim of the present study was to determine some markers of vascular function, including VEGF, active renin and prostaglandin E2 (PGE2) in patients with endocrine hypertension. The study comprised: 30 patients with primary aldosteronism; 32 patients with active Cushing's syndrome; 19 patients with pheochromocytoma; 22 patients with essential hypertension and 24 healthy volunteers. VEGF was significantly elevated in all groups of patients as compared to the controls. VEGF levels in patients with Cushing's syndrome were significantly higher than those in patients with essential hypertension and primary aldosteronism. We did not find significant differences in VEGF levels between patients with Conn adenomas and idiopathic aldosteronism as well as between patients with Cushing's disease and Cushing's syndrome. PGE2 levels were not significantly different among the groups. Active renin was significantly the lowest in patients with primary aldosteronism and significantly the highest in those with pheochromocytoma compared to controls. The level of active renin in patients with primary aldosteronism was significantly lower than in patients with Cushing's syndrome and pheochromocytoma. In conclusion, VEGF levels were significantly elevated in patients with endocrine hypertension due to glucocorticoid, mineralocorticoid and/or catecholamine excess. The highest VEGF levels were detected in patients with Cushing's syndrome. The latter is associated with accelerated development of atherosclerosis and increased cardiovascular risk. VEGF might contribute to the cardiovascular risk in this disease. This effect was not likely to be PGE2 mediated.

Circulating plasma levels of vascular endothelial growth factor in patients with sleep disordered breathing

Introduction: Cellular vascular endothelial growth factor (VEGF) expression is increased in response to regional hypoxia, however, contradictory results were reported on the effects of systemic hypoxemia on circulating VEGF levels. This study investigated plasma concentrations of VEGF in patients with a variable degree of overnight hypoxemia due to sleep disordered breathing (SDB). Methods: VEGF levels were assessed by ELISA in non-activated (VEGFbl) and thrombin stimulated platelet rich plasma (VEGFprp) of 45 patients with SDB: Group 1 patients with obstructive sleep apnea and an apnea–hypopnea index (AHI) > 15/h; Group 2 subjects with an AHI<5/h; Group 3 patients on CPAP treatment for sleep apnea. Results: 39 patients were included in the final analysis. Patients in Group 1 had a higher %time of sleep with SaO 2<90% and a significantly lower mean and minimum overnight oxygen saturation than subjects in Group 2 and patients in Group 3 ( P<0.05). Despite significant differences in overnight oxygenation, VEGFbl and VEGFprp concentrations were not significantly different between the three study groups. However, plasma levels of VEGFbl were significantly higher ( P=0.02) in SDB patients with arterial hypertension ( n=19; VEGFbl: 14.0±3.3 pg/ml ) than in those without arterial hypertension ( n=20; VEGFbl: 10.9±5.2 pg/ml ). There were no relationships between VEGF levels and polysomnographic oxygenation parameters. In univariate analysis we observed significant relationships for VEGFbl with BMI ( C:0.393; P<0.05) and serum fibrinogen ( C:0.399; P<0.05). Conclusions: Circulating plasma VEGF levels in patients with sleep disordered breathing may be unrelated to night time hypoxemia (257 Words).

Circulating vascular endothelial growth factor and active renin concentrations and prostaglandin E2 urinary excretion in patients with adrenal tumours.

The aim of the present study was to determine vascular endothelial growth factor (VEGF), prostaglandin E(2) (PGE(2)) and active renin levels in patients with hormonally active adrenal tumours. The study was comprised of 16 patients with primary aldosteronism, 13 patients with active Cushing's syndrome due to adrenal adenomas, 8 patients with adrenal carcinomas, 19 patients with phaeochromocytoma and 19 healthy volunteers. Active renin in plasma was determined by a two-site immunoradiometric assay. VEGF in sera samples and PGE(2) in 24-h urine were measured by ELISA. VEGF was significantly elevated in all the four groups of patients as compared with the controls. VEGF levels in patients with Cushing's syndrome were higher than those in patients with primary aldosteronism. Patients with adrenal carcinomas had the highest VEGF levels and the differences reached significance as compared with patients with primary aldosteronism and phaeochromocytoma. PGE(2) levels were not significantly different among groups. Active renin was significantly the lowest in patients with primary aldosteronism and significantly the highest in patients with phaeochromocytoma compared with the controls. Active renin in patients with primary aldosteronism was significantly lower than in those with Cushing's syndrome, phaeochromocytoma and adrenal carcinoma. Our data indicated that the mean level of VEGF in patients with all investigated adrenal tumours was significantly higher than in healthy controls. The cortisol-producing tumours appear to have increased angiogenic potential. Angiogenesis is probably associated not only with malignancy but also with functional activity of the adrenal tumors.

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.

Valores séricos de factor de crecimiento del endotelio vascular en pacientes con cáncer colorrectal y su significación pronóstica

Thirty per cent of patients with histologically node-negative colorectal cancer die from disseminated disease. Actually disease stage is the most useful prognostic parameter although it is not sufficient. Vascular endothelial growth factor (VEGF) is an angiogenic cytokine involved in the progression of tumors. In our study we tried to know the prognostic significance of pre and postoperative serum VEGF levels in patients with colorectal cancer. Cohort study that included 52 patients with colorectal cancer surgically treated in our Department from 1998 to 2000. Serum VEGF and CEA levels were determined the day before surgery and 30 days after it. Preoperative serum VEGF levels (428.5 [38.5] pg/ml) were higher than in control patients (p=0.008). Serum VEGF levels fallen significantly after surgery (343 [31.2] pg/ml; p=0.001). Pre and postoperative serum VEGF levels in poorly differentiated neoplasms were higher than in well differentiated ones (p=0.009 and p=0.008 respectively). Pre and postoperative serum CEA and VEGF levels were significantly associated with cancer relapse (p=0.037, p=0.017, p=0.048 and p=0.001, respectively). In multivariate analysis only postoperative serum VEGF levels were associated with colorectal cancer relapse (p=0.003; HR=1.007; 95% CI, 1.002-1.012). Pre and postoperative CEA levels (p<0.001 and p=0.001 respectively) and postoperative VEGF levels (p=0.001), were associated with mortality. In multivariate analysis only tumor stage (p=0.01) and postoperative serum VEGF levels (p=0.02) were associated with mortality. Postoperative serum VEGF determination and pre and postoperative CEA levels raise specificity and positive predictive values to 100% in relation to mortality. Pre and postoperative serum VEGF determination has prognostic significance, regardless of tumor stage, in patients with colorectal cancer. In survival methods, postoperative VEGF levels >343 pg/ml are significantly with tumor relapse and mortality. These results suggest the use of serum VEGF levels as a prognostic and monitoring factor besides CEA.

Vascular endothelial growth factor levels are increased and associated with disease activity in patients with Behçet's syndrome.

Vascular endothelial growth factor (VEGF) is a cytokine participating in inflammation with potent endothelial cell effects. It is produced by macrophages, neutrophils and vascular endothelial cells and can alter vessel permeability. Behçet's syndrome is a systemic inflammatory disorder with unknown etiology. Vascular endothelial dysfunction is one of the prominent features of the disease. We previously demonstrated the possible involvement of proinflammatory cytokines [tumor necrosis factor (TNF)-alpha, soluble interleukin-2 receptor (sIL-2R), interleukin (IL)-6 and IL-8], nitric oxide (NO) and adrenomedullin in the etiopathogenesis of Behçet's syndrome. Since VEGF expression is induced by these cytokines and VEGF itself is a potent stimulator of NO production with endothelial cell effects, this study aimed to investigate whether VEGF was affected during the course of Behçet's syndrome. We also assessed the possible involvement of VEGF in ocular Behçet's syndrome or in disease activity. This multicenter case-control study included a total of 39 patients with active (n = 22) or inactive (n = 17) Behçet's syndrome (mean age, 38.1 +/- 10.4 years; 21 men and 18 women) satisfying International Study Group criteria, and 15 healthy hospital-based control volunteers (mean age, 39.2 +/- 9.3 years; eight men and seven women) matched for age and gender from a similar ethnic background. Patients were examined by a dermatologist and an ophthalmologist with an interest in Behçet's syndrome. Plasma VEGF concentrations were measured using a newly established enzyme-linked immunosorbent assay. Clinical findings and acute-phase reactant parameters such as erythrocyte sedimentation rate, alpha1-antitrypsin, alpha2-macroglobulin, and neutrophil count were used to classify the disease in Behçet's patients as active or inactive. The Wilcoxon test or the Mann-Whitney U-test was used for statistical analysis as indicated and the results were expressed as mean +/- SD, with range. The mean plasma VEGF level in patients with Behçet's syndrome (291.9 +/- 97.1 pg/mL; range 121-532 pg/mL) was higher than that in control subjects (103.0 +/- 43.6 pg/mL; range 25-187 pg/mL) and the difference was significant (P < 0.001). Patients with active disease had significantly (P < 0.001) higher VEGF levels than patients with inactive disease (347.6 +/- 87.1 vs. 219.9 +/- 51.6 pg/mL). In addition, ocular Behçet's patients (n = 23) had higher VEGF levels (315.7 +/- 92.1 pg/mL) than nonocular patients (n = 16, 257.8 +/- 96.6 pg/mL) and the difference was of borderline significance (P = 0.041). The levels of all acute-phase reactant parameters were significantly higher in the active stage than in the inactive stage (for each, P < 0.01) or in control subjects (for each, P < 0.001). VEGF may participate in the course of Behçet's syndrome, especially in the active stage, and elevated levels of VEGF may be an additional risk factor for the development of ocular disease, contributing to poor visual outcome.

Elevated Levels of Serum Vascular Endothelial Growth Factor in Patients with Polycythaemia vera

Angiogenesis seems to be a prominent event of myeloproliferative diseases. There are few reported data on angiogenesis and the significance of its stimulator, the vascular endothelial growth factor (VEGF), in polycythaemia vera (PV). We report our observation of elevated serum VEGF levels in patients suffering from PV. Twenty patients with PV and 20 age-matched healthy subjects were enrolled. VEGF levels were measured by a quantitative sandwich enzyme immunoassay. Serum VEGF levels in PV were found to be very significantly higher than in healthy individuals (569.7 ± 101.2 vs. 164.7 ± 32.8 pg/ml, p = 0.001). We found no correlation between VEGF and haemoglobin, platelet or leucocyte counts in the patient group. Different therapeutic regimens had no influence on VEGF levels. However, in the control group, we observed a positive correlation between VEGF levels and platelet counts (r = 0.52, p = 0.02). Platelet counts did not differ between patients and healthy subjects. We also evaluated platelet-poor plasma VEGF levels in 10 patients and in all healthy individuals. We found very low levels of VEGF, approximately zero in most cases, in both groups and there was obviously no difference between the two groups. Our results indicate that VEGF is overproduced in PV. However, follow-up studies are needed to verify the role of this factor.

Increased vascular endothelial growth factor in acute eosinophilic pneumonia.

Acute eosinophilic pneumonia (AEP) is associated with the presence of diffuse pulmonary infiltrates on the chest radiograph and an increased number of eosinophils and an elevation of interleukin (IL)-5 levels in bronchoalveolar lavage (BAL) fluid. Vascular endothelial growth factor (VEGF) is a constitutively expressed protein encoded by messenger ribonucleic acid in human eosinophils and is released following stimulation with IL-5. However, the roles of IL-5 and VEGF in the pathogenesis or activity of this disease have not been clarified. The authors investigated the cells and the levels of these two factors in BAL fluid in five AEP patients and five normal controls before and after corticosteroid treatment. The absolute number of eosinophils-mL(-1), IL-5 and VEGF levels in patients before treatment were higher than in controls (53.8 versus 0.3 x 10(4) x mL(-1), 490.1 versus 5.2 pg x mL(-1) and 643.0 versus 133.9 pg x mL(-1), respectively). IL-5 and VEGF rapidly decreased to the control level in parallel with clinical improvement. The relationship between eosinophilia and IL-5 and VEGF levels was strongly significant. Elevated interleukin-5 in the lung may initiate the recruitment of eosinophils and enhance the release of mediators, such as vascular endothelial growth factor from eosinophils, which, in turn, increases the permeability of blood vessels.

Vascular endothelial growth factor in children with congenital heart disease

Background Children with cyanotic congenital heart disease may experience the development of abnormal vessels that become a source of significant morbidity. Abnormal vessel proliferation in these children may take several forms, including systemic-to-pulmonary collateral arteries, systemic-to-pulmonary venous collaterals, systemic venous collateral channels after bidirectional cavopulmonary anastomosis, and pulmonary arteriovenous malformations. However, no entity responsible for these abnormalities has been identified yet. This study determined whether children with cyanotic congenital heart disease have elevated serum levels of vascular endothelial growth factor (VEGF) and whether elevated VEGF correlated with these abnormal vessels. Methods Mean systemic room air oxygen saturation (SpO 2), blood cell counts (RBC), and serum VEGF levels were measured preoperatively. Samples were obtained from 61 children with acyanotic heart disease (group N) and 102 children with cyanotic heart disease (group C) before cardiac surgery. Postoperative catheterization was performed 1-month after the operation to evaluate the abnormal vessels in group C. Results The VEGF level was significantly elevated in group C (355.0 ± 287.1 pg/mL) compared with group N (203.0 ± 221.6 pg/mL; p < 0.001). VEGF levels in patients with a single ventricle associated with asplenia syndrome (n = 7) in group C were significantly elevated (711.9 ± 443.5 pg/mL) compared with other patients. There was no significant correlation between VEGF level and SpO 2 or RBC. Abnormal vessels were diagnosed in 19.6% (20/102) patients in group C. There was no difference in VEGF levels between the patients with abnormal vessels (336.8 ± 182.5 pg/mL) and the patients without abnormal vessels (359.1 ± 306.8 pg/mL). Conclusions Children with cyanotic heart disease have elevated systemic levels of VEGF, especially in those patients with a single ventricle associated with asplenia syndrome. There was no significant relationship in VEGF levels between the patients with abnormal vessels and without these vessels.