Serum Concentrations Of Angiogenic Factors Research Articles

Predictive value of the sFlt‑1/PlGF ratio in women with suspected preeclampsia: An update (Review).

Preeclampsia (PE) is a major complication of pregnancy with an incidence rate of 2‑8% and is a leading cause of maternal mortality and morbidity. The various consequences of severe preeclampsia for the fetus, neonate and child include intrauterine growth retardation (IUGR), fetal hypoxia, oligohydramnios, intrauterine fetal demise, increased perinatal mortality and morbidity, neurodevelopmental disorders and even irreversible brain damage (cerebral palsy). A number of studies have demonstrated that differences in maternal serum concentrations of angiogenic factors between preeclampsia and normotensive pregnancies can be used as biomarkers, either alone or in combination with other markers, to predict the development of PE. The presence in the maternal circulation of two proteins of placental origin, placental growth factor (PlGF) and soluble fms‑like tyrosine kinase 1 (sFlt‑1), has been shown to be of clinical value, as the sFlt‑1/PlGF ratio appears to be the optimal predictive tool for the development of PE. The measurement of their concentration in maternal serum in screening models, serves as predictive marker for the development of PE or IUGR later in gestation. However, further research is required to improve its clinical applicability and provide guidelines for its use worldwide to achieve more consistent clinical management of women with PE.

The performance of pre-delivery serum concentrations of angiogenic factors in predicting postpartum antihypertensive drug therapy following abdominal delivery in severe preeclampsia and normotensive pregnancy.

BackgroundThe imbalance between circulating concentrations of anti- and pro-angiogenic factors is usually intense in preeclampsia with severe features (sPE). It is possible that pre-delivery circulating levels of angiogenic factors in sPE may be associated with postpartum antihypertensive drug requirements.ObjectiveTo determine the predictive association between maternal pre-delivery serum concentrations of angiogenic factors and the use of ≥3 slow- and/or a rapid-acting antihypertensive drug therapy in sPE on postpartum days zero to three following caesarean delivery.Study designWomen with sPE (n = 50) and normotensive pregnancies (n = 90) were recruited prior to childbirth. Serum samples were obtained from each participant < 48 hours before delivery to assess the concentrations of placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) using the Roche Elecsys platform. Each participant was followed up on postpartum days zero, one, two and three to monitor BP and confirm antihypertensive treatment. The optimal cut-off thresholds of sFlt-1/PIGF ratio from receiver operating characteristic curve predictive of the antihypertensive therapy were subjected to diagnostic accuracy assessment.ResultsThe majority 58% (29/50) of sPE had multiple severe features of preeclampsia in the antenatal period with the commonest presentation being severe hypertension in 88% (44/50) of this group, followed by features of impending eclampsia which occurred in 42% (21/50). The median gestational age at delivery was 38 (Interquartile range, IQR 1) vs 36 (IQR 6) weeks, p < 0.001 in normotensive and sPE groups respectively. Notably, the median sFlt-1/PIGF ratio in normotensive and sPE groups were 7.3 (IQR 17.9) and 179.1 (IQR 271.2) respectively, p < 0.001. Of the 50 sPE participants, 34% (17/50) had early-onset preeclampsia. The median (IQR) of sFlt-1/PIGF in the early- and late-onset preeclampsia groups were 313.52 (502.25), and 166.59(195.37) respectively, p = 0.006. From postpartum days zero to three, 48% (24/50) of sPE received ≥ 3 slow- and/or a rapid-acting antihypertensive drug. However, the daily administration of ≥ 3 slow- and/or a rapid-acting antihypertensive drug in sPE were pre-delivery 26% (13/50), postpartum day zero 18% (9/50), postpartum day one 34% (17/50), postpartum day two 24% (12/50) and postpartum day three 20% (10/50). In sPE, the pre-delivery sFlt-1/PIGF ratio was predictive of administration of ≥3 slow- and/or a rapid-acting antihypertensive drug on postpartum days zero, one and two with the optimal cut-off ratio being ≥315.0, ≥181.5 and ≥ 267.8 respectively (sensitivity 72.7–75.0%, specificity 64.7–78.6%, positive predictive value 40.0–50.0% and negative predictive value 84.6% - 94.3%). The predictive performance of sFlt-1/PIG ratio on postpartum day 3 among the sPE was not statistically significant (area under receiver operating characteristic curve, 0.6; 95% CI, 0.3–0.8).ConclusionA pre-delivery sFlt-1/PIGF ratio (< 181.5) is a promising predictor for excluding the need for ≥3 slow- and/or a rapid-acting antihypertensive drug therapy in the immediate postpartum period in sPE.

Improved angiogenic activity of endothelial progenitor cell in diabetic patients treated with insulin plus metformin.

Type 2 diabetes (T2DM) is associated with an increased vascular disease. Moreover, endothelial progenitor cell (EPC) function is impaired in diabetic patients. Decreased EPC number plays a critical role in reduced endothelial repair and development of the vascular disorder. To determine the effect of metformin and insulin plus metformin on functional activity of EPCs, 130 participants were divided into three groups (group 1: healthy control; group 2: metformin; group 3: insulin plus metformin). The concentration of EPCs in the circulation was first quantified. Thereafter, circulating EPCs (cEPCs) were harvested and the biological features of these cells including proliferative, clonogenicity, tubulogenic, and migratory properties were analyzed after expansion. The serum protein levels of some proangiogenic factors were also measured. Our results showed greater numbers of cEPCs in control and in diabetic patients treated with insulin plus metformin than in metformin-treated patients. Insulin plus metformin therapy was associated with augmented proliferative, clonogenicity, migratory, and tubulogenic activity of cEPCs in patients with T2DM. Increased serum concentrations of angiogenic factors were also observed in patients treated with insulin plus metformin. Western blot analysis showed increased protein levels of pTie-2/Tie2 and Pakt/AKT in cEPCs harvested from T2DM, treated with insulin metformin plus. This study showed that treatment with insulin plus metformin in diabetic patients is associated with increased mobilization of EPCs into the circulation, with potential beneficial effect in vascular protection in diabetic patients.

Increased circulation mobilization of endothelial progenitor cells in preterm infants with retinopathy of prematurity

Retinopathy of prematurity (ROP) is a result of increased pathological neoangiogenesis of the retina in preterm infants. Cells responsible for the pathogenesis of ROP are unclear, but some evidence indicates that bone marrow derived cells are involved in this disorder. Endothelial progenitor cells (EPCs), play a role in angiogenesis in response to tissue ischemia or endothelial damage. In this study, the number of cEPCs in preterm infants with ROP was determined to identify whether the circulation mobilization of EPCs is associated with ROP. We evaluated 99 participants in this study: 22 preterm infants with ROP, 35 preterm infants without ROP, and 42 full-term infants. The release of EPCs in the circulation was first quantified. Thereafter, cEPCs were harvested and cultivated, then the biological features of these cells including migratory, proliferative, and tubulogenic activities were analyzed. The mRNA levels of some proangiogenic factors were also measured in preterm infants. Our results showed greater numbers of cEPCs in infants with ROP, which was associated with increased serum concentrations of angiogenic factors and with augmented proliferative, migratory, and tubulogenic activity of these cells. Western blotting showed increased protein levels of VEGF and HIF-α in cEPCs harvested from ROP infants. This study showed that ROP in preterm infants is associated with increased mobilization of EPCs into the circulation. Therefore, increased cEPCs along with elevated levels of angiogenic factors and tubulogenesis suggest that these cells may play a role in the development and progression of ROP.

Changes in serum concentrations of angiogenic factors in patients with type 2 diabetes mellitus

Forty-two patients with type 2 diabetes (DM group),23 type 2 diabetic patients with unstable angina pectoris (DM + UAP group),and 36 healthy subjects (control group) were enrolled in this study.Serum samples were collected for determining serum concentrations of vascular endothelial growth factor (VEGF),Angiopoietin (Ang)-1,Ang-2,angiogenin,angiostatin,basic fibroblast growth factor,and platelet-derived growth factor-BB using protein array technology.The results showed that there were no significant differences in serum concentrations of all 7 angiogenic factors between control group and DM group.Whereas,serum concentrations of V EGF and Ang-2 were significantly increased in DM + UAP group compared with control group [(3 532.10 ± 1 813.72vs 2 444.50 ± 1 152.21) pg/ml,(286.90-± 217.01 vs 171.92 ± 106.63) pg/ml,both P＜0.01].Pearson's correlation analysis revealed that serum concentrations of all 7 angiogenic factors were not related to HbA1C,fasting and 2 h postprandial plasma glucose,triglycerides,high density lipoprotein cholesterol,as well as low density lipoprotein cholesterol. Key words: Angiogenic factors ; Diabetes mellitus, type 2 ; Unstable angina pectoris; Protein array

AB0412 Plasma levels of angiogenic factors – association with clinical manifestations in systemic lupus erythematosus.

BackgroundThe data concerning systemic lupus erythematosus (SLE) and angiogenesis are relatively limited. Most of them are focused on the activity of the vascular endothelial growth factor (VEGF) as the key...

Changes of serum angiogenic factors concentrations in patients with diabetes and unstable angina pectoris

BackgroudDiabetic microvascular changes are considered to be influenced by angiogenic factors. As a compensatory mechanism, the expression of some angiogenic factors are elevated in ischemic myocardium. The aim of this study was to investigate the changes of serum angiogenic factors, and the association among these angiogenic factors, the severity of coronary artery stenosis and collateral vessels form in patients with diabetes and unstable angina pectoris (UAP).Methods42 patients with diabetes (diabetes group), 57 patients with UAP (UAP group), and 36 age-matched healthy people (control group) were selected. Serum concentrations of angiogenic factors were measured using cytokine array technology. The severity of coronary artery stenosis was scored using the angiographic Gensini score. Coronary collateral vessels were scored according to Rentrop's classification.ResultsNo significant differences in the serum concentrations of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), angiogenin, angiostatin, basic fibroblast growth factor (bFGF) and platelet-derived growth factor-BB (PDGF-BB) were detected between control group and diabetes group. But in patients with diabetes complicated with UAP and in patients with UAP without diabetes, serum concentrations of VEGF and Ang-2 were elevated (p < 0.01, p < 0.01). Only serum Ang-2 concentrations were significantly correlated with Gensini score (r=0.585, p < 0.001), left ventricular end diastolic diameter (r=0.501, p < 0.001), left ventricular end systolic diameter (r=0.563, p < 0.001) and left ventricular ejection fraction (r=−0.523, p < 0.001).ConclusionSerum concentrations of VEGF and Ang-2 were increased, and diabetes didn’t affect this increases in patients with UAP. Serum Ang-2 concentrations were correlated with the severity of coronary artery stenosis.

O2. Serum concentrations of angiogenic factors as predictors of severity of preeclampsia, in Colombian population

dictors of severity of preeclampsia, in Colombian population M.C. Paez , N.C. Serrano , L.A. Diaz , M.A. Beltran , R. Ortiz , A. Monterrosa , W. Saldarriaga , C. Mesa , J.E. Sanin , G. Monsalve , E. Guio , P.K. Bautista , C. Colmenares , C. Vargas , M.E. Hincapie , E. Staines , A. Hingorani , J.P. Casas h,i ( Biomedical Research Center, Faculty of Health, UNAB, Colombia, Universidad de Cartagena, Colombia, Universidad del Valle, Colombia, Universidad CES, Medellin, Colombia, Universidad Pontificie Bolivariana, Medellin, Colombia, f Clinica del Prado, Medellˇn, Colombia, Universidad Industrial de Santander – UIS, Bucaramanga, Colombia, h Faculty of Epidemiology and Public Health, London School of Hygiene & Tropical Medicine, UK, i Department of Epidemiology and Public Health, University College London, UK)

Pancreatitis aguda

The present review discusses eight studies, selected for their clinical importance in the field of acute pancreatitis (AP). A multicenter clinical trial demonstrated that treatment of infected pancreatic necrosis through drainage, followed by video-assisted retroperitoneal debridement in patients with poor clinical course, was superior to classical open surgery in terms of costs and complications. A retrospective study analyzed the radiation from computed tomography received by patients with necrotizing AP and warned of the high dose administered, which could have significant carcinogenic effects. A multicenter retrospective study confirmed the utility of measuring blood urea nitrogen at admission and at 24 hours in predicting mortality due to AP. A prospective study of fluid therapy reported that inadequate or excess fluid administration in the first 24 hours of admission were related to poor outcome. Two studies analyzed the bedside index for severity in AP (BISAP) score at admission; this scoring system was useful in AP in general but not in the subgroup of patients requiring admission to the intensive care unit. Lastly, two studies showed the highly promising prognostic value of determining serum concentrations of angiogenic factors in AP.

Significance of vascular endothelial growth factor, interleukin-18 and nitric oxide in patients with breast cancer: correlation with carbohydrate antigen 15.3

The aim of this study was to determine serum concentrations of angiogenic factors including vascular endothelial growth factor (VEGF), interleukin 18 (IL-18) and nitric oxide (NO) in patients with breast cancer and to evaluate whether these factors will be correlated with CA 15.3, as a routine tumor marker for breast cancer or not. This study was conducted on 44 patients with breast cancer and 15 healthy individuals as a control group. The results demonstrated significant increase in serum IL-18, NO and CA 15.3 levels in sera of breast cancer patients when compared to those of the control group (P < 0.001, P = 0.016 and P < 0.001, respectively). However, the mean serum level of VEGF in patients as showed insignificant increase compared to that of the controls was not significant (P = 0.311). Sensitivity of CA 15.3, VEGF, IL-18 and NO to detect patients with disease was 52.2, 21.3, 77.2 and 70.4 %, respectively. In addition, positive status of serum CA 15.3 and/or IL-18 was found in 39 out of 44 (88.6 %) patients, and the positive status of serum CA 15.3 and/or NO was only found in 35 out of 44 (79.5 %). In conclusion, the simultaneous determination of IL-18 or NO in combination with the CA 15.3 may increase the sensitivity to diagnose breast cancer and may aid in disease prognosis.

Serum levels of angiogenic factors in early breast cancer remain close to normal

The study which we performed was to determine serum concentrations of angiogenic factors including VEGF, angiogenin and TGF-beta 1 in early stage breast cancer patients. These parameters were measured by ELISA in sera of 90 patients with breast cancer and 75 healthy controls. The mean serum VEGF concentration in patients compared to controls was not significantly different (0.33 ng/mL vs 0.43 ng/mL, respectively; p = 0.156). Likewise, the insignificant change in mean values in patients vs controls was also observed for serum TGF-beta 1 (0.19 ng/mL vs 0.19 ng/mL, respectively; p = 0.215) and serum angiogenin (243.24 ng/mL vs 244.5 ng/mL, respectively; p = 0.976). Statistically significant correlation was found only between the tests, such as VEGF and angiogenin in patients who were included in the study ( p < 0.001). In conclusion, we couldn't find any diagnostic value between the early stage breast cancer and the three angiogenic parameters.

Decline in angiogenic factors, such as interleukin-8, indicates response to chemotherapy of metastatic melanoma

Serum concentrations of angiogenic factors have been reported to correlate with tumour burden and prognosis in metastatic melanoma. The present study was performed to assess the value of angiogenic factors in serum in indicating response or failure to chemotherapy and immunochemotherapy in stage IV melanoma. Thirty-five patients suffering from stage IV melanoma according to the American Joint Committee on Cancer (AJCC) criteria were included in this prospective study. Before and following chemotherapy or immunochemotherapy, serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF-AB), vascular cell adhesion molecule-1 (VCAM-1) and interleukin-8 (IL-8) were measured. Staging examinations following chemotherapy revealed 15 patients with response to therapy (complete response, partial response, stable disease), 14 patients with progressive disease and six patients with mixed response. Patients who responded to therapy showed a significant decrease in the serum level of IL-8 at the time of staging examinations, whereas patients with progressive disease did not. Following chemotherapy, serum concentrations of PDGF-AB had significantly decreased in both patients with response and patients with progressive disease. Comparing the VEGF and bFGF levels of responders and non-responders after a single administration of cytostatics showed significantly lower concentrations in patients with response to therapy. In all patients, a high intra- and inter-individual variability of serum values was observed during application of therapy. It can be concluded that low IL-8 serum levels after chemotherapy indicate response to chemotherapy in stage IV melanoma patients. The persistence of elevated serum levels of VEGF and bFGF following the initial cytostatic administration may help to identify patients resistant to chemotherapy. The distinct variability of serum levels indicates that processes other than tumour angiogenesis also influence the serum concentration of the examined angiogenic factors.

Circulating Angiogenic Factors and the Risk of Preeclampsia

The cause of preeclampsia remains unclear. Limited data suggest that excess circulating soluble fms-like tyrosine kinase 1 (sFlt-1), which binds placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), may have a pathogenic role. We performed a nested case-control study within the Calcium for Preeclampsia Prevention trial, which involved healthy nulliparous women. Each woman with preeclampsia was matched to one normotensive control. A total of 120 pairs of women were randomly chosen. Serum concentrations of angiogenic factors (total sFlt-1, free PlGF, and free VEGF) were measured throughout pregnancy; there were a total of 655 serum specimens. The data were analyzed cross-sectionally within intervals of gestational age and according to the time before the onset of preeclampsia. During the last two months of pregnancy in the normotensive controls, the level of sFlt-1 increased and the level of PlGF decreased. These changes occurred earlier and were more pronounced in the women in whom preeclampsia later developed. The sFlt-1 level increased beginning approximately five weeks before the onset of preeclampsia. At the onset of clinical disease, the mean serum level in the women with preeclampsia was 4382 pg per milliliter, as compared with 1643 pg per milliliter in controls with fetuses of similar gestational age (P<0.001). The PlGF levels were significantly lower in the women who later had preeclampsia than in the controls beginning at 13 to 16 weeks of gestation (mean, 90 pg per milliliter vs. 142 pg per milliliter, P=0.01), with the greatest difference occurring during the weeks before the onset of preeclampsia, coincident with the increase in the sFlt-1 level. Alterations in the levels of sFlt-1 and free PlGF were greater in women with an earlier onset of preeclampsia and in women in whom preeclampsia was associated with a small-for-gestational-age infant. Increased levels of sFlt-1 and reduced levels of PlGF predict the subsequent development of preeclampsia.