Plasma Vascular Endothelial Growth Factor In Patients Research Articles

The expressions of CTLA-4 and PD-1 on CD(4)(+) T cells and the level of plasma VEGF in patients with obstructive sleep apnea hypopnea syndrome

Objective: CD(4)(+)T cells, cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and vascular endothelial growth factor (VEGF) are associated with cancer development. The aim of the present study was to investigate the expression of CTLA-4, PD-1 and VEGF in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: From January 2017 to January 2018, a total of 47 first-visit outpatients were recruited in the Sleep and Respiratory Disorder Center of Guangdong Provincial People's Hospital, and were divided into control group (N=17, mean age 54±12 years), mild-to-moderate OSAHS group (N=15, mean age 54±12 years) and severe OSAHS group (N=15, mean age 56±13 years). Venous blood was collected, plasma and cells were isolated, the expressions of PD-1 and CTLA-4 on the surface of CD(4)(+)T cells were detected by flow cytometry, and plasma VEGF was measured by enzyme linked immunosorbent assay. Results: The proportion of CD(4)(+)T cells in control group, mild-to-moderate OSAHS group and severe OSAHS group were respectively(38±8)%, (35±8)% and (38±6)% (F=1.228, P>0.05). The expression of CTLA-4 on CD(4)(+)T cells were respectively [1.13 (0.59~1.78)]%, [0.45 (0.16~1.43)]% and [0.87(0.47~1.46)]% (H=2.205, P>0.05). The expression of PD-1 on CD(4)(+)T cells were respectively [4.24 (2.12~6.03)]%, [3.54(2.69~5.09)]% and [3.31(1.67~8.25)]% (H=0.541, P>0.05). The concentrations of VEGF in control group, mild-to-moderate OSAHS group and severe OSAHS group were statistically different [(395.16±87.78) ng/L vs (452.85±107.97) ng/L vs (546.42±199.27) ng/L, F=4.827, P=0.013]. Compared with the control group, VEGF concentration was significantly increased in the severe OSAHS group(P<0.01). VEGF concentration was correlated negatively with the lowest SpO(2) (r (s)=-0.480,P=0.001), but positively with apnea-hypopnea index(r (s)=0.403, P=0.005), oxygen desaturation index (r (s)=0.378, P=0.010) and proportion of SpO(2) less than or equal to 90% of total sleep time(r (s)=0.547, P=0.000 3). Conclusion: There was no significant difference of PD-1 and CTLA-4 expression on CD(4)(+)T cells in patients with and without OSAHS. The expression of VEGF was elevated in OSAHS patients, and increased with the severity of OSAHS and hypoxia.

Vascular endothelial growth factor during hypoglycemia in patients with type 1 diabetes mellitus: relation to cognitive function and renin-angiotensin system activity

In healthy adults, levels of vascular endothelial growth factor (VEGF) increase in response to mild hypoglycemia. VEGF is implicated in glucose transport over the blood-brain barrier, and the increase during hypoglycemia has been positively correlated with preservation of cognitive function during hypoglycemia. High activity in the renin-angiotensin system (RAS) is associated with an increased risk of severe hypoglycemia in patients with type 1 diabetes mellitus. Renin-angiotensin system possibly exerts its mechanism in hypoglycemia via VEGF. We studied the impact of mild hypoglycemia on plasma VEGF in patients with type 1 diabetes mellitus and high or low RAS activity and analyzed associations between VEGF levels and cognitive function during hypoglycemia. Eighteen patients with type 1 diabetes mellitus—9 with high and 9 with low RAS activity—underwent a single-blinded, placebo-controlled, crossover study with either mild hypoglycemia or stable glycemia. Cognitive function was assessed by the California Cognitive Assessment Package and the Alzheimer Quick Test. Nadir plasma glucose was 2.2 (0.3) mmol/L. During the control study, plasma VEGF did not change. During hypoglycemia, plasma VEGF increased from 39 to 58 pg/L in the high-RAS group ( P = .004) and from 76 to 109 pg/L in the low-RAS group ( P = .01), with no difference between RAS groups ( P = .9). A weak association between reduced preservation of cognitive function during hypoglycemia and low VEGF response was observed. Plasma VEGF levels increase during mild, short-term hypoglycemia in patients with type 1 diabetes mellitus. The VEGF response is not dependent on RAS activity and only weakly associated with preservation of cognitive function during hypoglycemia. Thus, the previously described association between low RAS activity and better cognitive performance during hypoglycemia does not seem to be mediated by VEGF.

Vascular endothelial growth factor and platelets in primary (essential) thrombocythaemia

Primary or essential thrombocythaemia (PT), a rare myeloproliferative disorder, is characterised by high platelet numbers, an increased risk of thrombosis and haemorrhage, and a reduced life expectancy. In addition to thrombocytosis, additional platelet abnormalities include alterations in soluble P-selectin (sP-selectin), platelet P-selectin (pP-selectin) and platelet factor 4 (Musolino et al, 2000; Villmow et al, 2002). Vascular endothelial growth factor (VEGF) is an angiogenic product of several cells, including endothelial cells and platelets (Blann et al, 2004), and increased levels (thereby possibly implying alterations in angiogenesis), are present in PT and other myeloproliferative disorders (Di Raimondo et al, 2001; Musolino et al, 2002). The implications of this finding are unknown. Furthermore, the source of this VEGF is unclear and could have pathophysiological and/or therapeutic connotations. We therefore set out to test the hypothesis that platelets are a major source of plasma VEGF in patients with PT. To do this we measured levels of VEGF in and plasma and platelet lysates in a simple cross-sectional study comparing patients to healthy age- and sex-matched controls, and compared levels to those of sP-selectin. This study was a sub-analysis of a group of patients previously studied (Blann et al, 2004). Patients were recruited if they fulfilled diagnostic criteria of PT. Almost all were being treated with combinations of aspirin (75 mg/d) and anagrelide (mean ± SD 1·6 ± 0·6 mg/d) or hydroxycarbimide (0·95 ± 0·3 g/d). Patients were compared with 15 age- and sex-matched healthy controls recruited from hospital staff. All subjects gave written informed consent and the study had the approval of the Ethics Committee of City Hospital, Birmingham, UK. In the routine Haematology laboratory, EDTA-plasma was tested for platelet count (Advia, Bayer, Newbury, UK). In the research laboratory, VEGF and sP-selectin were measured in citrated plasma by enzyme-linked immunosorbent assay (ELISA; R&D Systems, Abingdon, UK). The total mass of VEGF per platelet was estimated by lysing a set number of thrice-washed platelets with 0·5% Triton X-100 (Sigma, Poole, UK), and then measuring VEGF in the lysate by ELISA to give the mean mass of P-selectin per platelet (Kamath et al, 2002). The results are shown in Table I. As expected (Musolino et al, 2000; Villmow et al, 2002; Blann et al, 2004), patients had a higher platelet count, sP-selectin and VEGF than controls. However, there was no difference in the mass of VEGF per platelet. Within the patient group, there were no significant Spearman's correlations between the platelet count and VEGF (r = −0·059, P = 0·752), nor between sP-selectin and VEGF (r = 0·081, P = 0·659). However, the platelet count correlated with sP-selectin (r = 0·373, P = 0·036). Increased levels of plasma VEGF in PT are an established finding and the presence of this angiogenic growth factor in platelets naturally leads to the question of whether or not this is important. Interest lies in the possibility that platelet VEGF may contribute to angiogenesis within the bone marrow and thus the disease process. The observations of the present study suggest this may not be the case. First, despite differences in plasma levels, there was no difference in platelet VEGF between the patients and matched controls. Secondly, neither platelet nor plasma VEGF correlated significantly with either the platelet count, or with sP-selectin. We therefore suggest that raised plasma VEGF in PT is not the direct consequence of altered platelet activity.

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.

Carbohydrate intake relates to plasma VEGF in patients with type 2 diabetes

Vascular endothelial growth factor (VEGF) a potent polypeptide regulator of blood vessel function is related with various pathophysiological changes in type 2 diabetes, but surprisingly VEGF was not yet studied in association to food intake or body weight in diabetes. VEGF has been suggested to enhance glucose transport across the blood-brain barrier (BBB) and may thereby increase brain glucose supply. Increased brain glucose concentrations are known to suppress food intake and body weight by its feedback on hypothalamic regulation centres. Here we hypothesized that VEGF concentrations may relate to food intake and body weight in humans. A population-based cohort of 190 subjects with type 2 diabetes was examined regarding their food intake pattern at a breakfast buffet. VEGF and additional other clinical parameters were measured and correlated with food intake and body weight. We found that subjects with higher concentrations of plasma VEGF (≥ 31 pg/ml; median) had less carbohydrate intake (30.9±1.5 vs. 37.1g±1.5; P=0.002) and a slightly lower body weight (86.2±1.6kg vs. 90.1±1.5kg; P=0.046) than those with lower VEGF concentrations(<31 pg/ml; median). With respect to VEGF's action on BBB permeability and glucose transport, we propose an enhanced brain glucose feedback as possible reason for this association. Our finding that plasma VEGF relates to carbohydrate intake and body weight in patients with type 2 diabetes may provide a new aspect of food intake regulation and energy homeostasis.

Plasma vascular endothelial growth factor is useful in assessing progression of breast cancer post surgery and during adjuvant treatment

Vascular endothelial growth factor (VEGF) has been shown to induce angiogenesis in vivo and in vitro. However, the association of plasma VEGF with tumor histopathology in high risk groups such as African American and non-white Hispanic women with breast cancer is not well understood. There is limited information on the prognostic relevance of plasma VEGF in patients who have had surgery and adjuvant treatment for breast cancer. In this study, we measured plasma VEGF from 125 minority women with primary breast tumor removal and were completing adjuvant treatment. The control group consisted of 20 subjects without cancer. We examined the association between plasma VEGF and other tumor characteristics such as steroid hormone receptors, tumor size, regional nodes, stage, recurrence, and overall survival. Our results confirmed that plasma VEGF levels were significantly higher in breast cancer patients than normal subjects. Plasma VEGF level increased in patients with increase in tumor size, and at late stage III/IV disease. Univariate analysis showed plasma VEGF to be a significant predictor of overall survival (RR=2.5, p=0.02). Multivariate analysis showed plasma VEGF not only to be an independent predictor of overall survival (RR=4.6, p=0.02) but also of local recurrence (RR=6.0, p=0.04). Tamoxifen in combination with CMF or CAF can reduce plasma VEGF level in patients with estrogen receptor positive tumor but not in estrogen receptor negative tumor. Our findings suggest that plasma VEGF should be considered as a tumor marker for breast cancer progression, and inhibitors of angiogenesis should be factored into the treatment protocol for patients who demonstrate increase in plasma VEGF levels at any stage of the disease.

Plasma VEGF concentration can predict the tumor angiogenic capacity in non-small cell lung cancer.

We assessed the clinical utility of circulating angiogenic factors as a predictor for tumor angiogenesis in primary lung cancer. Circulating vascular endothelial growth factor (VEGF) and intratumoral VEGF were assessed by enzyme-linked immuno-sorbent assay (ELISA). There was a significant increase in the mean value of both plasma and serum VEGF concentration in primary lung cancer patients (n=97) compared to those of healthy controls (n=59). There was a significant correlation between plasma VEGF levels and microvessel density (MVD), and also between plasma VEGF and intratumoral VEGF levels. Plasma VEGF in patients with lung cancer appears to be a useful indicator of tumor angiogenesis.