Lower Plasma Vascular Endothelial Growth Factor Levels Research Articles

Plasma apelin and vascular endothelial growth factor levels in preterm infants: relationship to neonatal respiratory distress syndrome

Aim The study aimed to determine the association between cord plasma levels of apelin and vascular endothelial growth factor (VEGF) with respiratory distress syndrome (RDS) in preterm infants. Methods This case-control study included 120 preterm infants admitted to the neonatal intensive care unit of our hospital between January 2019 and January 2020. The infants were divided into RDS (n = 60) and non-RDS groups (n = 60). The cord plasma apelin and VEGF levels, perinatal characteristics, and neonatal complications were compared between the two groups. Results The plasma apelin levels in the RDS group were significantly higher than in the non-RDS group (158.9 ± 24.8 vs. 125.2 ± 18.2 pg/mL, respectively), whereas VEGF levels in the non-RDS group were significantly higher than in the RDS group (187.4 ± 28.5 vs. 245.1 ± 44.8 pg/mL, respectively) (both p < .001). Infants with more severe RDS had higher plasma apelin levels and lower plasma VEGF levels. In the receiver operating characteristic curve analysis for the prediction of RDS, a cutoff of 148.4 pg/mL for apelin level yielded a sensitivity of 63.3% and a specificity of 95.0%, whereas a cutoff of 214.2 pg/mL for VEGF level showed a sensitivity of 86.7% and a specificity of 75.0%. Apelin levels were negatively correlated with VEGF levels in infants with RDS (r = 0.84, p < .001). Conclusion Differences in cord plasma apelin and VEGF levels may aid in the early diagnosis and treatment of RDS in preterm infants.

40P - Vascular endothelial growth factor in colorectal cancer pathology, survival and treatment

BackgroundAngiogenesis (the growth of new blood vessels) is important for tumour invasion and metastasis in order for a tumour to grow beyond a few millimetres in size. Vascular endothelial growth factor (VEGF) is thought to be the predominant angiogenic factor in colorectal and other cancers. As a result, numerous studies have looked at VEGF expression in colorectal cancer patients and several therapeutic agents have been trialled that target the VEGF pathway. MethodsVEGF levels were determined in 100 paired tumour and normal colorectal tissue samples (1998-2001) and 75 pre-operative plasma samples (2000-2002) by ELISA. Tissue (pg/mg protein) and plasma VEGF levels (pg/ml) were correlated with the tumour pathology. Survival analysis was performed for disease-free and overall 15-year survival (Kaplan Meier, p<0.05). The study had ethics approval. ResultsVEGF levels were significantly up-regulated in colorectal tumour tissue compared to normal tissue. The median VEGF levels were 288 (range, 30-4,156) pg/mg protein for tumour, 38 (0-833) for normal colon and 90 (0-1,262) pg/ml for pre-operative plasma samples. Tumour levels of VEGF correlated with the tumour depth, differentiation and whether the tumour had undergone lymphatic invasion e.g. well differentiated, 230 (79-1,348), moderate 392 (30-4,156) and poorly differentiated 685 (88-2,612)pg/mg protein. Plasma VEGF levels significantly correlated with tumour differentiation and vascular invasion,e.g. 211 (14-889) vascular invasion and 80 (0-785)pg/ml, no vascular invasion. The 15-year survival status for patients with tissue samples was 30% were alive and well, 1% was alive with recurrence and 69% had died. For the 75 plasma patients; 27% patients were alive and well with the remaining 67% having died. VEGF levels in plasma but not tissue samples significantly correlated with both disease-free and overall 15-year survival, with patients with low plasma VEGF levels having a better survival outcome (p<0.05, Kaplan Meier). ConclusionsVEGF levels in both colorectal tumour tissue and pre-operative plasma samples correlated with the tumour pathology. However, only pre-operative plasma VEGF levels correlated with disease-free and overall 15-year survival. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Correlation between vascular endothelial growth factor and long-term prognosis in patients with acute myocardial infarction.

The aim of the present study was to investigate the correlation between plasma the levels of vascular endothelial growth factor (VEGF) and major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI). A total of 124 patients with AMI undergoing emergency percutaneous coronary intervention (PCI) were selected, and plasma VEGF levels were measured 7 days after the onset of AMI using an enzyme-linked immunosorbent assay. The patients were divided into the L (≤190 pg/ml VEGF) and H (>190 pg/ml VEGF) groups, and were followed up every 2 months for an average of 12 months. MACE were recorded during follow-up. On the basis of these results, the patients were further divided into the MACE and non-MACE (N-MACE) groups, and the serum VEGF concentration was compared between the two groups. At the 6-month follow-up, the incidence of MACE in the H group was found to be significantly reduced compared with the L group. The serum VEGF concentration in the N-MACE group was significantly higher compared with the MACE group. Multinomial logistic regression revealed that reduced VEGF levels (β=1.243; 95% CI, 1.018-1.326; P=0.026) were independent risk factors for MACE. In conclusion, high plasma VEGF levels at 7 days after AMI onset facilitate the long-term prognosis in the same infarct zone in patients with AMI, while low plasma VEGF levels are independent risk factors for MACE.

Impact of Low Levels of Vascular Endothelial Growth Factor After Myocardial Infarction on 6-Month Clinical Outcome

Vascular endothelial growth factor (VEGF) is induced by myocardial ischemia and is thought to facilitate cardiovascular repair after acute myocardial infarction (AMI). However, the association between the plasma VEGF levels and clinical outcome in AMI patients is unclear. We evaluated 879 AMI patients undergoing successful primary revascularization within 24h of symptom onset. The patients were classified into 3 groups according to tertiles of plasma VEGF levels at 7 days after the onset of AMI. Major adverse cardiovascular and cerebrovascular events (MACCE), defined as cardiac death, recurrent acute coronary syndrome, hospital readmission for heart failure, or stroke, were assessed during the 6-month follow-up period. The incidence of MACCE was the least frequent in the middle tertile. Compared to the middle tertile, patients in the low tertile were at a significantly higher risk for MACCE even after adjusting for baseline characteristics (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.18-6.06, P=0.019). An absence of statin treatment before onset and a younger age (HR 0.54, 0.87; 95%CI 0.33-0.90, 0.76-0.99; P=0.017, 0.037; respectively) were significantly associated with low VEGF. Low plasma VEGF levels at 7 days after the onset of AMI were associated with a significantly increased risk for MACCE during 6 months of follow-up.

Preliminary Results Concerning the Prognosis Value of Vascular Endothelial Growth Factor (VEGF) in Chronic Myeloid Leukemia Patients Treated with Imatinib Mesylate.

Increased angiogenesis in bone marrow (BM) is one of the characteristics of chronic myeloid leukemia (CML), a clonal myeloproliferative disorder which expresses a chimeric Bcr/Abl protein. The therapeutic strategy in CML has been totally modified with the development of Imatinib Mesylate (STI571), a specific inhibitor of Bcr/Abl tyrosine kinase activity. Previously, we studied the effect of Imatinib on the Vascular Endothelial Growth Factor (VEGF), one of the most potent regulators of angiogenesis (1). Thus, we demonstrated, for the first time, the decrease in VEGF production in CML patients treated with Imatinib. It pointed out the potential prognostic value of determining the VEGF plasma level of patients in order to follow the evolution of this hematologic malignancy. Actually, we showed that low plasma VEGF levels could be one of the characteristics of complete cytogenetic remission.However, investigations with a larger number of patients were necessary to evaluate the potential of VEGF levels in the monitoring of CML patients treated with Imatinib. So, we analyzed VEGF plasma level in patients treated in the SPIRIT, the CML French Group phase III, multicenter, open-label, prospective trial. Patients are randomized between the 3 experimental arms [IM 400mg daily in combination with Peg-IFN-α2a (Peg-IFNα2a, 90 μg weekly) or with Ara-C (20 mg/m2/day, days 15–28 of 28-day cycles) or IM 600mg daily] and the reference arm, IM 400mg daily. The Endpoint are overall survival (primary), rate and duration of hematologic, cytogenetic and molecular responses and tolerability. This VEGF evaluation is based on a cohort of 110 pts [median age 51 yrs (19–81); Sokal distribution : 30% of pts low, 37% intermediate, and 33% high]. Males predominated (62%) and percentage of patients enrolled in IM 400mg, IM 600mg, IM 400 with Ara-C and IM 400mg with Peg-IFN arm is respectively 28%, 28%, 24% and 30%. At diagnosis, the median of VEGF plasma level is 945 pg/ml (range: 42.3–4001.5). After 3 months of treatment, the median of VEGF level decreases significantly (p<0.05) to 116.4 pg/ml (range: 6.7–2780). After 6, 9, 12 months of treatment, the median of VEGF level was stabilized at respectively 104 pg/ml (range: 17.9–2244.9), 88.3 pg/ml (range: 21.2–907.4), 99 pg/ml (range: 22.1–689,2).To determine prognosis value of VEGF we correlated the results with the cytogenetic and molecular response.

DNA Sequence Variation In The VEGF Gene And Plasma VEGF Protein Levels

Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen involved in the process of angiogenesis. VEGF has been shown to be influenced by exercise and our laboratory has previously identified associations between DNA sequence variation in the VEGF gene and skeletal muscle capillarity and maximal oxygen consumption. PURPOSE The aim of this project was to determine if DNA sequence variation in the VEGF gene is associated with plasma VEGF protein levels. METHODS Subjects included 75 healthy, sedentary men and women, 50–75 years of age. Genomic DNA was extracted from peripheral lymphocytes and RFLP genotyping was performed on the C-2578A, G-634C, C-7T, and C936T variants in the VEGF gene. RESULTS The G-634C and C936T polymorphisms did not appear to be associated with plasma VEGF protein levels. Subjects of AA genotype at the C-2578A polymorphism exhibited ∼54% higher plasma VEGF protein levels than did subjects of AC or CC genotype (29.1±4.5 vs. 18.9±1.9 and 18.8±2.3, respectively, p < 0.05). Subjects of CC genotype at the C-7T polymorphism exhibited ∼28% lower plasma VEGF levels than did carriers of the T-allele (CT and TT genotype) (17.5±1.7 vs. 24.4±2.4, respectively, P = 0.02). CONCLUSIONS DNA sequence variation in the VEGF gene appears to be associated with circulating plasma VEGF levels in older men and women. Supported by NIH AG17474, AG15389, AG22791, and T32-A00268.

The VEGF +405 CC Promoter Polymorphism is Associated With an Impaired Prognosis in Patients With Chronic Heart Failure: A MERIT-HF Substudy

Background A common polymorphism positioned at +405 of the vascular endothelial growth factor (VEGF) gene is known to influence VEGF protein production. In contrast, a second polymorphism, positioned at −460 polymorphism, has no reported functional effects. VEGF is linked to angiogenesis and might directly influence the clinical outcome of patients with chronic heart failure (CHF). We investigated the association between two VEGF polymorphisms and morbidity and mortality in patients with CHF. Methods and Results VEGF promoter polymorphisms +405 and −460 were examined in 596 CHF patients enrolled in the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF) study and in 187 healthy controls. In CHF patients, a risk ratio for each genotype was calculated using the combined endpoint of all-cause mortality or hospitalization. The allele frequencies of the +405 and −460 polymorphisms for the CHF cohort and for 187 healthy controls were not significantly different. However, the presence of the +405 CC genotype (frequency 0.14) was independently associated with an adverse outcome as described by the MERIT study combined endpoint compared with the +405 GG genotype (risk ratio 1.65; 95%CI 1.03–2.64; P = .039). The −460 polymorphism was not associated with an altered prognosis ( P = .60). Conclusion Our results indicate that the VEGF +405 CC genotype is associated with an adverse clinical outcome in patients with CHF. This genotype has been associated with lower plasma VEGF levels, suggesting a possible mechanism of action for the gene variant. This belief is further supported by the fact that the VEGF −460 polymorphism, which does not affect plasma VEGF levels, did not adversely affect the prognosis.