Serum Levels Of Angiogenic Factors Research Articles

Imaging of Angiogenesis in White Matter Hyperintensities.

Background White matter hyperintensities (WMHs) are areas of increased signal intensity on T2-weighted magnetic resonance imaging (MRI). WMH penumbra may be a potential target for early intervention in WMHs. We explored the relationship between angiogenesis and WMH penumbra in patients with WMHs. Methods and Results Twenty-one patients with confluent WMHs of Fazekas grade ≥2 were included. All the participants underwent 68Ga-NOTA-PRGD2 positron emission tomography/magnetic resonance imaging. WMH penumbra was analyzed with masks created for the WMH and 7 normal-appearing white matter layers; each layer was dilated away from the WMH by 2 mm. Angiogenesis array and ELISA were used to detect the serum levels of angiogenic factors, inflammatory factors, HIF-1 alpha, and S100B. Fourteen patients with increased 68Ga-NOTA-PRGD2 maximum standardized uptake (>0.17) were classified into group 2. Seven patients with maximum standardized uptake ≤0.17 were classified as group 1. WMH volume and serum levels of integrin αvβ3, vascular endothelial growth factor receptor 22, and interleukin-1β tended to be higher in group 2 than in group 1. In group 2, 68Ga-NOTA-PRGD2 uptake was significantly increased at the border between the WMH and normal-appearing white matter than in WMHs (P=0.004). The structure penumbra, defined by fractional anisotropy, was wider in group 2 (8 mm) than in group 1 (2 mm). The cerebral blood flow penumbra was 12 mm in both groups. Angiogenesis showed a correlation with reduced cerebral blood flow and microstructure integrity. Conclusions Our study provides evidence that angiogenesis occurs in the WMH penumbra. Further studies are warranted to verify the effect of angiogenesis on WMH growth.

Changes in serum angiogenic factors among patients with acute pain and subacute pain.

Screening serum biomarkers for acute and subacute pain is important for precise pain management. This study aimed to examine serum levels of angiogenic factors in patients with acute and subacute pain as potential biomarkers. Serum samples were collected from 12 healthy controls, 20 patients with postherpetic neuralgia (PHN), 4 with low back pain (LBP), and 1 with trigeminal neuralgia (TN). Pain intensity in these patients was evaluated using the visual analog scale (VAS). The serum concentrations of 11 angiogenic biomarkers were examined by Milliplex Map Human Angiogenesis Magnetic Bead Panel 2. The pain assessment from VAS showed that all patients showed moderate and severe pain. Among 11 angiogenic factors, osteopontin (OPN), thrombospondin-2 (TSP-2), soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1), soluble urokinase-type plasminogen activator receptor (suPAR), and soluble epidermal growth factor receptors (sErbB2) were up-regulated and soluble interleukin-6 receptor α (sIL-6Rα) were down-regulated in patients with pain compared to the healthy participants (all P-values were < 0.005). Moreover, a linear regression model showed that the serum OPN concentration was correlated with pain intensity in patients with PHN (P = 0.03). There was no significant difference between the serum concentration of soluble epidermal growth factor receptors, sErbB3, soluble AXL, tenascin, and soluble neuropilin-1 in patients with acute and subacute pain and that of healthy controls. The results of this study provided new valuable insights into our understanding of angiogenic factors that may contribute to as mechanistic biomarkers of pain, and reveal the pathophysiological mechanism of pain.Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2200061775.

Effect of Daclatasvir and Sofosbuvir Therapy on Serum Levels of Angiogenic Factors: A Prospective Cohort Study

Background: Direct-acting antiviral agents therapy is considered a breakthrough in hepatology due to high rates of sustained virologic response in all patients including those with decompensated cirrhosis. However, impact of Direct-acting antiviral agents-induced sustained virologic response on hepatocellular carcinoma development remains conflicting.&#x0D; Aims: This study aimed at evaluating the change in circulating levels of vascular endothelial growth factor and transforming growth factor-β1, the main angiogenic factors involved in hepatocarcinogenesis process, in cirrhotic patients achieved sustained virologic response after Direct-acting antiviral agents therapy.&#x0D; Study Design: This was a prospective, single-center, cohort study.&#x0D; Place and Duration of Study: Patients were recruited from the outpatient clinic of National Liver Institute, which considered a tertiary referral center in Menoufia University, Egypt (September 2018 to February 2019).&#x0D; Methodology: Forty-five decompensated cirrhotic hepatitis C virus infected patients with no history of hepatocellular carcinoma participated in the study. All patients received 60mg oral daclatasvir and 400mg oral sofosbuvir once daily for 12 or 24 weeks with or without ribavirin. Serum levels of vascular endothelial growth factor and transforming growth factor-β1 were measured at baseline and 12 weeks after the end of therapy.&#x0D; Results: The median serum levels of vascular endothelial growth factor showed a non-statistically significant increase (from 1123 ng/L to 1269 ng/L, P = 0.126). But, transforming growth factor-β1 median serum levels exhibited a non-statistically significant reduction (from 13.22 ng/ml to 12.44 ng/ml, P = 0.163) 12 weeks after treatment.&#x0D; Conclusion: Our findings show direct-acting antiviral agents therapy do not affect vascular endothelial growth factor and transforming growth factor-β1 serum levels. But, a larger scale prospective cohort study on an extended follow-up period is recommended.

Shared changes in angiogenic factors across gastrointestinal vascular conditions: A pilot study.

BACKGROUNDNeovascularisation is common to a variety of gastrointestinal (GI) disorders with differing aetiologies and presentations; usually affecting adults above 60 years. Shared angiogenic factors modulated by disease specific elements could be a common denominator and represent novel diagnostic and therapeutic targets. As yet, assessment of angiogenic factors across several GI vascular disorders associated with recurrent bleeding and anaemia has not been reported.AIMTo assess serum levels of angiogenic factors in several intestinal vascular disorders.METHODSA case control study was performed in Tallaght University Hospital in patients with endoscopically proven small bowel angiodysplasia (SBA), portal hypertensive gastropathy (PHG), gastric antral vascular ectasia (GAVE) and non-bleeding, non-anaemic controls. Using enzyme-linked immunosorbent assay, concentrations of Angiopoietin 1 (Ang-1), Ang-2 and vascular endothelial growth factor (VEGF) were measured from 2 serum tubes of blood following informed consent. The relative expression of Ang-1 and Ang-2 and Ang-1/2 ratio was calculated and compared between groups. Statistical analysis was applied using a t-test, and a P value of < 0.05 was considered significant.RESULTSTo date 44 samples were tested: 10 SBA, 11 PHG, 8 GAVE and 15 controls. Mean age 60 (range 20-85) years and 20 (45%) were males. Controls were significantly younger (49 years vs 66 years, P = 0.0005). There was no difference in VEGF levels between the groups (P = 0.6). SBA, PHG and GAVE Ang-1 levels were similar and were significantly lower than controls, (P = 0.0002, 95%CI: 241 to 701). Ang-2 levels were statistically higher in PHG and GAVE groups compared to controls (P = 0.01, 95%CI: 77.8 to 668) and as a result, also had a lower Ang-1/2 ratios compared to controls. While SBA Ang-2 levels were higher than controls, this did not reach statistical significance. Neither age nor haemoglobin level, which was similar between disease groups, could explain the difference. In addition, the median Ang-1/Ang-2 ratio for all patients was found to be significantly lower compared to controls, 8 vs 28 respectively, P = 0.001, 95%CI: -27.55 to -7.12.CONCLUSIONOur novel pilot study suggests common alterations in Ang-1 and Ang-2 levels across several GI vascular disorders. Differences in Ang-1/Ang-2 ratios among vascular disorders compared to controls suggest disease-specific modulation.

Serum Levels of Angiogenic Factors Distinguish Between Women with Preeclampsia and Normotensive Pregnant Women But Not Severity of Preeclampsia in an Obstetric Center in Turkey.

BackgroundThis study aimed to compare serum levels of vascular endothelial growth factor (VEGF) and the VEGF receptors, VEGFR-1 and VEGFR-2, free placental growth factor (fPGF), endostatin, and serum pregnancy-associated plasma protein-A (PAPP-A) levels in women with mild and severe preeclampsia and healthy pregnant women.Material/MethodsA included patients diagnosed with mild preeclampsia (n=32), severe preeclampsia (n=32), and healthy pregnant women (n=24). Serum levels of VEGF-A, VEGFR-1, VEGFR-2, fPGF, endostatin, and PAPP-A levels were measured by enzyme-linked immunosorbent assay (ELISA).ResultsIn women with mild and severe preeclampsia, the gestation age at birth and birth weight were found to be significantly lower than the control group (p<0.001). Serum levels of endostatin, VEGFR-1, and VEGF-A levels were significantly increased in pregnant women with preeclampsia compared with healthy pregnant women (p<0.001). Serum levels of PAPP-A, VEGFR-2, and fPGF were significantly higher in healthy pregnant women when compared with women with preeclampsia (p=0.024, p<0.001, and p<0.001, respectively), but there were no significant differences between women with mild and severe preeclampsia.ConclusionsReduced serum levels of the angiogenic factors PAPP-A, VEGFR-2, and fPGF distinguished between women with preeclampsia and normotensive pregnant women but did not significantly distinguish between mild and severe preeclampsia.

Angiogenic Potential, Circulating Angiogenic Factors and Insulin Resistance in Subjects with Obesity.

Altered vascular function and pathological angiogenesis are important factors common to the development of obesity and obesity-associated diseases. Most human studies relating obesity and angiogenesis have compared levels of angiogenic factors in obesity without looking at the serum angiogenic capacity which reflects the balance between the effects of angiogenic and angiostatic factors. Therefore, in this cross-sectional study, the serum angiogenic potential and levels of angiogenic factors in serum of obese (BMI > 25kg/m2) and lean subjects (BMI < 23kg/m2), with no history of obesity associated co-morbidities, were assessed. Serum angiogenic potential was significantly higher (p < 0.0001) in both male (n = 67) and female (n = 35) obese subjects and showed a positive correlation (r = 0.4, p < 0.0001) with BMI. Serum levels of the angiogenic factors, vascular endothelial growth factor (VEGF) and angiopoietin were significantly higher in obese subjects. Levels of angiostatic factors such as angiostatin, endostatin were not altered in obese male subjects but were elevated in female obese subjects. Angiogenic potential and levels of VEGF did not vary in obese subjects with high HOMA-IR compared to obese subjects with low HOMA-IR. These results suggest that the angiogenic potential of serum was elevated in obesity and that insulin resistance may not contribute to the increased angiogenic potential in obesity.

224. Measurement of serum angiogenic markers at the 2nd trimester can predict fetal growth restriction (FGR) mothers who will subsequently develop preeclampsia (PE)

Objectives It is reported that FGR and PE are associated with abnormal profiles of angiogenic markers in maternal circulation. Mothers with FGR fetuses are at increased risks for developing PE. The aim of our study is to determine the cut-off levels of maternal serum angiogenic markers to develop PE subsequently among FGR mothers. Methods This study included women with singleton pregnancies diagnosed with FGR before 24 weeks of gestation (n = 50). The protocol was approved by ethics committees and participants provided written informed consents. The serum levels of PlGF, sFlt-1, sEndoglin and sFlt-1/PlGF ratio were measured at 20–24 weeks of gestation. The cut-off value of each angiogenic factor was determined by ROC curve analysis for identifying mothers with FGR at risk of developing PE. Results The prevalence of patients with FGR preceding PE was 40% (n = 20/50). The mean of onset period of subsequent PE was 30.1 ± 4.8 weeks of gestation. The mean gestational age at delivery of PE + FGR group and FGR only group was 32.4 ± 5.4 weeks vs 37.0 ± 4.9 weeks respectively. We compared serum levels of angiogenic factors among PE + FGR and FGR only groups. In the PE + FGR group, the level of PlGF was significantly decreased, and the levels of sFlt-1, sEndoglin, and sFlt-1/PlGF were significantly increased as compared with FGR only group. The optimal cut-off levels were PlGF level 1829.3 pg/mL (AUC = 0.884), sEndoglin level >7.41 ng/mL (AUC = 0.967), and sFlt-1/PlGF ratio >7.42(AUC = 0.941). sEndoglin and sFlt-1/PlGF ratio were the most powerful predictors for developing PEwith sensitivity of 88.9% and 86.7%, and specificity of 92.6 and 92.0% respectively. Conclusions Angiogenic factors measured in maternal sera between 20 and 24 weeks of gestation can identify mothers diagnosed with FGR who subsequently develop PE. Measurement of these markers may contribute to the risk assessment of mothers with FGR, and their clinical outcomes.

New arguments for beneficial effects of alpha-lipoic acid on the cardiovascular system in the course of type 2 diabetes

PurposeAlpha-lipoic acid (ALA), widely known as an antioxidant, modifies also serum levels of angiogenic factors in type 2 diabetic patients. These pharmacological activities may influence the status of the cardiovascular system. Taking into consideration that diabetes is related to the increased cardiovascular risk we investigated several effects of ALA on angiogenic factors in the myocardium and in the aortal wall using a rat model of type 2 diabetes. MethodsDiabetes was induced in Wistar rats by a fat-rich diet and by intraperitoneal injection of a small dose of streptozotocin (30 mg/kg). Animals were divided into 3 groups: ALA-treated type 2 diabetes rat model, placebo-treated type 2 diabetes rat model and placebo-treated non-diabetic rats. ALA was administered orally once a day, 20 mg/kg, for 8 consecutive weeks. mRNA VEGF, VEGF-R1 and VEGF-R2 expression was measured in the myocardium and the aortal wall, simultaneously with circulating VEGF and circulating endothelial cells (cEC) and endothelial progenitor cells (cEPC). ResultsALA induced pro-angiogenic effect in the myocardium of rats with diabetes increasing mRNA VEGF expression and decreasing mRNA VEGFR-1 expression, while in the aortal wall ALA increased mRNA VEGFR-2 and VEGFR-1 expression. cVEGF in the ALA-treated group was higher comparing to both control groups. It was revealed that cEC percentage in the ALA-treated group was decreased with no effect on the percentage of cEPC. ConclusionsIn summary, the current data provide novel findings about potential beneficial effects of ALA on angiogenic factors in the cardiovascular system, especially on myocardium, in the course of type 2 diabetes.

Cell-to-cell contact with HTLV-1-infected T cell reduces dendritic cell immune functions and contributes to infection in trans

Alpha-lipoic acid (ALA), widely known as an antioxidant, modifies also serum levels of angiogenic factors in type 2 diabetic patients. These pharmacological activities may influence the status of the cardiovascular system. Taking into consideration that diabetes is related to the increased cardiovascular risk we investigated several effects of ALA on angiogenic factors in the myocardium and in the aortal wall using a rat model of type 2 diabetes.Diabetes was induced in Wistar rats by a fat-rich diet and by intraperitoneal injection of a small dose of streptozotocin (30 mg/kg). Animals were divided into 3 groups: ALA-treated type 2 diabetes rat model, placebo-treated type 2 diabetes rat model and placebo-treated non-diabetic rats. ALA was administered orally once a day, 20 mg/kg, for 8 consecutive weeks. mRNA VEGF, VEGF-R1 and VEGF-R2 expression was measured in the myocardium and the aortal wall, simultaneously with circulating VEGF and circulating endothelial cells (cEC) and endothelial progenitor cells (cEPC).ALA induced pro-angiogenic effect in the myocardium of rats with diabetes increasing mRNA VEGF expression and decreasing mRNA VEGFR-1 expression, while in the aortal wall ALA increased mRNA VEGFR-2 and VEGFR-1 expression. cVEGF in the ALA-treated group was higher comparing to both control groups. It was revealed that cEC percentage in the ALA-treated group was decreased with no effect on the percentage of cEPC.In summary, the current data provide novel findings about potential beneficial effects of ALA on angiogenic factors in the cardiovascular system, especially on myocardium, in the course of type 2 diabetes.

Myocardial performance index in hypertensive disorders of pregnancy: The relationship between blood pressures and angiogenic factors

ABSTRACTObjective: To study the association between cardiac function measured by myocardial performance index (MPI), blood pressures and angiogenic factors measured at the time of echocardiography in patients with and without hypertensive disorders of pregnancy (HDP).Methods: We prospectively studied 189 pregnant women and evaluated whether changes in cardiac function observed on echocardiography were correlated with higher blood pressures and whether higher blood pressures were associated with antiangiogenic proteins (soluble fms-like tyrosine kinase, sFlt1; soluble endoglin, sEng). Comprehensive echocardiograms, including measurement of MPI, were performed on all patients. sFlt1 and sEng levels were measured using enzyme-linked immunosorbent assay.Results: Overall, 189 patients were divided into tertiles based on mean arterial pressure (MAP). The MPI was worst in tertile 3 (0.50 ± 0.15) compared to tertile 1 (0.42 ± 0.10), p = 0.0004. sFlt1 (pg/ml) and sEng (ng/ml) were highest in tertile 3 compared to tertile 1: 15055.37 vs. 1623.01 and 33.06 vs. 8.15, respectively, with p-value <0.001. In crude multivariate regression analysis, MAP was positively correlated with MPI (r = 0.32, p < 0.001), GLS (r = 0.54, p < 0.001), sFlt1 (r = 0.60, p < 0.001) and sEng (r = 0.61, p < 0.001). After adjustment for confounders, these relationships persisted between MAP and MPI (r = 0.31, p = 0.0003), GLS (r = 0.46, p < 0.001), sFlt1 (r = 0.56, p < 0.001) and sEng (r = 0.58, p < 0.001).Conclusion: Mean arterial pressure correlates with worsening cardiac function as measured by MPI and serum levels of angiogenic factors. Further studies are needed to evaluate whether a reduction in blood pressure will reverse changes in MPI or reduce levels of angiogenic proteins seen among women with HDP.

Circulating serum levels of angiopoietin-1 and angiopoietin-2 in nasopharynx and larynx carcinoma patients

We aimed to determine the serum levels of angiogenic factors, namely angiopoietins, in nasopharyngeal and laryngeal carcinoma patients. We also aimed to seek the relation of these molecules with tumor grade and their utility as diagnostic biomarkers. We evaluated angiopoietin 1 and 2 levels innasopharynx and larynx cancer patients before treatment. Angiopoietin 2 levels were significantly elevated in larynx carcinoma patients and tended to be elevated in nasopharynx cancer patients compared with healthy controls. However, angiopoietin 1 levels were similar in cancer patients and controls. Angiopoietin 1 levels were significantly higher in nasopharyngeal cancer patients with advanced stages compared to earlier stages. On the other hand, angiopoietin 2 levels were similar in advanced and earlier stage cancer patients.

Pathogenesis of preeclampsia.

Preeclampsia is a gestational kidney disease characterized by glomerular endothelial injury, leading to maternal hypertension and proteinuria. If not addressed promptly, there is significant maternal and fetal morbidity and mortality. When severe, this disorder can cause hepatic and neurologic dysfunction. Understandably, this placental disease enters the focus of the obstetrician first; however, with progression, the nephrologist can also be enlisted. Typical complications include acute kidney injury, refractory hypertension, and acute pulmonary edema. This review summarizes recent literature on the pathogenesis of this condition and will highlight new diagnostic and therapeutic options for preeclampsia. Over the past decade, the role of soluble vascular factors in preeclampsia has shed light on the mechanism underlying this disease. During the last 2 years, several new therapeutics have been developed that target implicated circulating angiogenic factors, including soluble fms-like tyrosine kinase 1, an endogenous vascular endothelial growth factor inhibitor. Serum levels of angiogenic factors have been correlated with a constellation of hemodynamic and pathophysiologic changes. Thus, circulating levels of these factors may serve both diagnostic and prognostic purposes. Overall, our understanding of preeclampsia has developed significantly and the future holds promise for mechanism-based novel diagnostics and therapeutics.

Antenatal Corticosteroids Impact the Inflammatory Rather Than the Antiangiogenic Profile of Women With Preeclampsia

Circulating antiangiogenic factors and proinflammatory cytokines are implicated in the pathogenesis of preeclampsia. This study was performed to test the hypothesis that steroids modify the balance of inflammatory and proangiogenic and antiangiogenic factors that potentially contribute to the patient's evolving clinical state. Seventy singleton women, admitted for antenatal corticosteroid treatment, were enrolled prospectively. The study group consisted of 45 hypertensive women: chronic hypertension (n=6), severe preeclampsia (n=32), and superimposed preeclampsia (n=7). Normotensive women with shortened cervix (<2.5 cm) served as controls (n=25). Maternal blood samples of preeclampsia cases were obtained before steroids and then serially up until delivery. A clinical severity score was designed to clinically monitor disease progression. Serum levels of angiogenic factors (soluble fms-like tyrosine kinase-1 [sFlt-1], placental growth factor [PlGF], soluble endoglin [sEng]), endothelin-1 (ET-1), and proinflammatory markers (IL-6, C-reactive protein [CRP]) were assessed before and after steroids. Soluble IL-2 receptor (sIL-2R) and total immunoglobulins (IgG) were measured as markers of T- and B-cell activation, respectively. Steroid treatment coincided with a transient improvement in clinical manifestations of preeclampsia. A significant decrease in IL-6 and CRP was observed although levels of sIL-2R and IgG remained unchanged. Antenatal corticosteroids did not influence the levels of angiogenic factors but ET-1 levels registered a short-lived increase poststeroids. Although a reduction in specific inflammatory mediators in response to antenatal steroids may account for the transient improvement in clinical signs of preeclampsia, inflammation is unlikely to be the major contributor to severe preeclampsia or useful for therapeutic targeting.

Enhanced stromal syndecan-1 expression is an independent risk factor for poor survival in bladder cancer

In this study, we assessed the changes and prognostic relevance of syndecan-1 (SDC1) tissue and serum levels in bladder cancer (BC). SDC1 levels were analyzed in 213 samples (119 paraffin-embedded and 79 serum samples of BC patients and 15 controls) using immunohistochemistry and enzyme-linked immunosorbent assay. Results were correlated with clinicopathological characteristics and follow-up data, as well as previously determined serum levels of angiogenic factors (basic fibroblast growth factor, endostatin, angiostatin, angiopoietin, vascular endothelial growth factor, Tie2 and MMP-7). SDC1 staining was present in the cell membrane of normal bladder epithelium and non-muscle-invasive BC cells but was absent in a significant proportion of muscle-invasive carcinomas (P < .001). In contrast, stromal SDC1 expression was enhanced in muscle-invasive compared to non-muscle-invasive BCs (P = .001). Serum concentrations of the SDC1 ectodomain were higher in muscle-invasive BCs compared to controls or non-muscle-invasive carcinomas (P < .001 each). Lymph node-positive cases had the highest SDC1 serum concentrations (P < .001). SDC1 expression in stromal cells was independently associated with survival (hazard ratio = 2.034, 95% confidence interval 1.176-3.519, P = .011). SDC1 serum concentrations correlated with those of endostatin and matrix metalloproteinase 7. Loss of SDC1 in tumor cells and the parallel increase of serum SDC1 ectodomain concentration in high-stage, high-grade BCs suggest the involvement of SDC1 shedding in BC progression. In addition, high preoperative SDC1 serum levels may help to identify patients with lymph node metastases, supporting therapeutic decision-making. Presence of SDC1 in tumor stroma is an independent risk factor for patient survival and may therefore be used to select patients for more aggressive therapy.

Serum levels of angiogenic and anti-angiogenic factors: their prognostic relevance in locally advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a prototype tumor wherein angiogenesis plays a vital role in its progression. The role of VEGF, a major angiogenic factor in HCC is known; however, the role of anti-angiogenic factors simultaneously with the angiogenic factors has not been studied before. Hence, in this study, the serum levels of major angiogenic [Vascular Endothelial Growth Factor (VEGF), angiopoietin-2 (Ang-2)] and anti-angiogenic (endostatin, angiostatin) factors were analyzed and correlated with clinico-radiological features and with outcome. A total of 150 patients (50 HCC, 50 cirrhosis and 50 chronic hepatitis) and 50 healthy controls were enrolled in this study. Serum levels of VEGF, Ang-2, endostatin, and angiostatin were estimated by enzyme-linked immunosorbent assay. HCC shows significantly elevated serum levels of angiogenic factors VEGF and Ang-2 and of anti-angiogenic factors endostatin and angiostatin. ROC curve analysis for serum VEGF yielded an optimal cut-off value of 225.14 pg/ml, with a sensitivity of 78 % and specificity of 84.7 % for a diagnosis of HCC and its distinction from other group. Using this value, the univariate and multivariate analysis revealed significantly poor outcome in patients with higher levels of serum VEGF (p = 0.009). Combinatorial analysis revealed that patients with higher levels of both angiogenic and anti-angiogenic factors showed poor outcome. Serum VEGF correlates with poor survival of HCC patients and, therefore, serves as a non-invasive biomarker of poor prognosis. Moreover, elevated levels of anti-angiogenic factors occur endogenously in HCC patients.

Clinical outcome, proteome kinetics and angiogenic factors in serum after thermoablation of colorectal liver metastases

BackgroundThermoablation is used to treat patients with unresectable colorectal liver metastases (CRLM). We analyze clinical outcome, proteome kinetics and angiogenic markers in patients treated by cryosurgical ablation (CSA) or radiofrequency ablation (RFA).Methods205 patients underwent CSA (n = 20), RFA (n = 22), partial hepatectomy (PH, n = 134) or were found truly unresectable (n = 29). Clinical outcome, proteome transitions and angiogenic response in serum were analyzed at various time points after ablation.ResultMedian overall survival in CSA patients (17.6 months) was worse (p < 0.0001) when compared to RFA treated patients (51.7 months) and patients after PH (43.4 months). The complication rate was higher in the CSA group (50%) as compared to the RFA group (22%). Proteomics analyses showed consistently more changes in serum protein abundance with CSA compared to RFA. In the first four days after ablation a pro-angiogenic serum response occurred.ConclusionsRFA of CRLM is superior to CSA with a median survival which equals survival in patients after PH. Proteomics analyses suggests a more aggravated serum response to CSA compared to RFA. Thermoablation is associated with changes in serum levels of angiogenic factors favouring a pro-angiogenic environment, but without differences between RFA and CSA.

A triploid partial mole placenta from paternal isodisomy with a diploid fetus derived from one sperm and one oocyte may have caused angiogenic imbalance leading to preeclampsia-like symptoms at 19 weeks of gestation

Partial hydatidiform mole with a normal fetus is extremely rare. A 30-year-old woman presented at 19 weeks gestation with clinical manifestations of severe preeclampsia. The fetus revealed a normal 46,XX karyotype and the placenta revealed triploid 69,XXX from paternal isodisomy. Microsatellite analysis revealed that the fetus and the triploid partial mole were derived from one sperm and one oocyte, followed by duplication of paternal chromosomes in only a trophectodermal cell. The maternal serum levels of angiogenic factors were extremely high compared with those reported in preeclampsia, suggesting an angiogenic imbalance may have caused preeclampsia-like symptoms before 20 weeks of gestation.

First-trimester serum soluble fms-like tyrosine kinase-1, free vascular endothelial growth factor, placental growth factor and uterine artery Doppler in preeclampsia

To compare the first-trimester serum concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1), free vascular endothelial growth factor (free-VEGF), placental growth factor (PlGF), and uterine artery pulsatility index (PI) in women who later developed preeclampsia (PE). Prospectively collected maternal serum samples were evaluated for sFlt-1, free VEGF, and PlGF levels in 63 cases who later developed PE compared with 252 unaffected controls. Serum levels of these angiogenic factors were measured using Quantikine immunoassays. Both univariate and multivariate analyses were used to evaluate the association between angiogenic factors and PE. The relationship between the angiogenic factors and mean maternal uterine artery PI was also evaluated. Maternal serum sFlt-1 levels were not significantly different between the cases and controls. Mean free-VEGF levels were significantly higher in women destined to develop PE compared with the controls (P=0.04), and mean PlGF levels were significantly lower in women who later developed PE (P=0.01). There was no significant correlation between maternal mean uterine artery PI and angiogenic factors evaluated. Receiver-operating characteristic curves revealed that none of the factors were clinically useful for prediction in the first trimester of PE. Despite some significant differences in the first-trimester serum levels of angiogenic factors, our models suggest that these factors are not clinically useful for prediction in women who later developed PE.

Assessment of serum levels of angiogenic factors in dizygotic twin infants with and without retinopathy of prematurity

The aim of the study was to evaluate the plasma concentrations of vascular endothelial growth factor (VEGF-A), its soluble receptors VEGFR-1 and VEGFR-2, insulin like growth factor (IGF-1) and soluble Tie-2 in twin infants with and without retinopathy of prematurity (ROP). Eleven pairs of twin infants (total 22 infants) were included in the study: There were 11 infants with advanced stage ROP in the study group and 11 infants with no ROP in the control group. Before time-point measurements, the peripheral venous blood samples were first centrifuged, and the plasma was then stored at -70°C. The plasma concentrations of the angiogenic factors were measured by using high sensitivity enzyme-linked immunosorbent assay (ELISA) kits. The average gestational age of the infants at the time of birth and the time at which the serum samples were collected were 30.5±2.3 and 37.5±2.5 weeks, respectively. The average serum levels of all the angiogenic factors were higher in infants with ROP, but the differences were not statistically significant (p>0.05). In this study, serum samples of twins with and without ROP were evaluated simultaneously. The time of serum sampling in the study group corresponded to the period of phase 2 ROP. Therefore, there appeared to be no difference between the ROP group and the control group. J. Exp. Clin. Med., 2013; 30:39-43

The role of angiogenic factors and their soluble receptors in acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) associated with critical illness

BackgroundAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by a disruption of the endothelium and alveolar epithelial barriers involving increased microvascular permeability, thus resulting in the set of protein-rich pulmonary edema. Angiogenic factors and their receptors, including vascular endothelial growth factor (VEGF)/VEGF-receptor (VEGFR) and the angiopoietin (Ang)/Tie2 signaling pathways, play pivotal roles in both angiogenesis and microvascular permeability. The aim of the study was to assess the relationship between angiogenic factors, their soluble receptors and ALI/ARDS associated with critically ill patients, including sepsis, severe trauma, and post-cardiac arrest syndrome (PCAS).MethodsOne hundred fifty-nine critically ill patients, including 50 patients with sepsis, 57 patients with severe trauma and 52 resuscitated after out-of-hospital cardiac arrest, were divided into three subgroups: including 25 ALI patients, 101 ARDS patients and 22 non-ALI/ARDS patients. The serum levels of angiogenic factors were measured at the time of admission (day 1), as well as day 3 and day 5 and then were compared among the ALI, ARDS and non-ALI/ARDS groups. Their predictive values for developing ALI/ARDS and 28-day mortality were evaluated.ResultsHigher levels of sVEGFR1 and Ang2 were observed in the ALI and ARDS patients than in the non-ALI/ARDS patients during the entire study period. The Ang2/Ang1 ratio in the ARDS group was also significantly higher than that in the non-ALI/ADRS group. The sVEGFR2 levels in the ARDS group on day 1 were significantly lower than those of the non-ALI/ADRS group. In addition, significant positive correlations were seen between the sVEGFR1, Ang2, Ang2/Ang1, and the development of ALI/ARDS in critical illness. There were also significant negative correlations between the minimal value of sVEGFR2, the maximal value of Ang1 and the ALI/ARDS group. In particular, sVEGFR2 and Ang2 were independent predictors of developing ALI/ARDS. Moreover, Ang2 and sVEGFR2 also independently predicted the mortality in ALI/ARDS patients.ConclusionsAngiogenic factors and their soluble receptors, particularly sVEGFR2 and Ang2, are thus considered to be valuable predictive biomarkers in the development of ALI/ARDS associated with critical illness and mortality in ALI/ARDS patients.