Serum Ang-2 Levels Research Articles

Capillaroscopic patterns in patients with systemic sclerosis, psoriasis and alopecia and their correlations with serum concentrations of several angiogenic markers

Abstract Introduction. Capillaroscopy is a non-invasive imaging method that allows cutaneous microcirculation to be analyzed. During the last decades, a diagnostic and prognostic potential of nailfold capillaroscopy (NVC) has been gaining increasing appreciation. The main indications include Raynaud phenomenon and scleroderma spectrum diseases, however the usefulness of this technique is also suggested in a variety of non-rheumatic diseases. Aim. To assess capillaroscopic patterns in systemic scleroderma (SSc), psoriasis (PV), psoriatic arthritis (PsA), alopecia areata (AA) and androgenetic alopecia. To evaluate serum levels of several endothelial and angiogenic markers, and their relation to capillaroscopic pattern. Material and methods. There were evaluated 295 patients with systemic scleroderma (SSc), psoriasis (PV), psoriatic arthritis (PsA), alopecia areata (AA) and androgenetic alopecia, as well as age- and sex-matched controls, were examined. In each subject, NVC was performed and serum concentration levels of several angiogenic markers. Results. In SSc three NVC patterns: early, active and late were distinguished. Angiopoietin-2 concentrations were higher and andothelial microparticles were lower in patients with late NVC pattern. We found several differences between the NVC pattern in PV and PsA. No correlations between NVC pattern and serum levels of angiogenic markers were revealed. In AA, we distinguished both normal and abnormal NVC patterns, although the normal patterns were more frequent. Branching capillaries and features of neoformation were often present in patients with the abnormal pattern. In androgenetic alopecia, the normal NVC pattern was most frequently present, however, we found several statistically significant capillarosopic alterations, like branching capillaries, features of neoformation and altered distribution of capillaries. Discussion and Conclusions. Serum levels of Ang-2 and EMPs may reflect capillary damage in SSc. NVC pattern varies between PV and PsA patients. The presence of abnormal NVC patterns in alopecia patients might show the role of disturbances in microcirculation in the diseases. Further studies are required to confirm the hypothesis.

Serum angiopoietin-2 is associated with angiopathy in type 2 diabetes mellitus

PurposeThe aim of the present study was to investigate the association of serum levels of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) with angiopathy in type 2 diabetes mellitus (T2DM). MethodsThe group studied comprised of 120 patients with T2DM (68 males and 52 females), included macroangiopathy complications, microvascular disease and diabetic without vascular disease. The control group consisted of 50 healthy blood donors. Ang-1, Ang-2, fasting plasma glucose (FBG), fasting insulin (FINS) and HbA1c were assessed. ResultsThe serum Ang-2 levels of T2DM patients with angiopathy were found to be significantly higher compared to patients without angiopathy. Ang-2 levels were significantly positively correlated with homeostasis model assessment for insulin resistance (HOMA-IR) and glycosylated hemoglobin A1c (HbA1c) (r=0.577 and 0.504, respectively, P<0.01). In contrast, there was no significant correlation between Ang-1 levels and HOMA-IR (P>0.05). In multivariable logistic regression analysis, Ang-2 levels (P=0.02) were found to be independently associated with patients with T2DM angiopathy. ConclusionsAn association between the Ang-2 and T2DM with vascular complications was found.

Urinary angiopoietin-2 is associated with albuminuria in patients with type 2 diabetes mellitus.

Aims. To evaluate the levels of angiopoietin-1 (Ang-1), Ang-2, and vascular endothelial growth factor (VEGF) in serum and urine, and their association with albuminuria in patients with type 2 diabetes mellitus. Methods. In 113 type 2 diabetic patients with normoalbuminuria, microalbuminuria, and macroalbuminuria and 30 healthy controls, the levels of Ang-1, Ang-2, and VEGF in serum and urine were measured by enzyme-linked immunosorbent assay (ELISA). Results. Urinary and serum levels of Ang-2 were significantly higher in diabetic patients with normoalbuminuria than in healthy controls. Increased urinary Ang-2 level was positively associated with the degree of albuminuria. Urinary Ang-1 levels were significantly higher in normoalbuminuria patients and lower in macroalbuminuria patients than in controls. The levels of urinary VEGF increased in the albuminuria subgroup, though serum levels of Ang-1 and VEGF did not change. Urinary Ang-2 levels were correlated positively with albuminuria and negatively with glomerular filtration rate (GFR). Stepwise multiple regression analysis identified albuminuria (P < 0.001) and GFR (P = 0.001) as significant predictors of urinary Ang-2. Conclusions. Our data suggest that urinary Ang-2 is stepwise increased with renal damage in patients with type 2 diabetes mellitus and is associated with albuminuria.

Serum Angiopoietin-2 as Marker of Plasma Leakage in Dengue Viral Infection

Background. The immunopathology of DHF/DSS is yet completely understood. Angiopoietin-2 (Ang-2) produced by endothelial cell could promote vascular leakage by disrupting endothelial junction. Few studies reported the role of Ang-2 in dengue viral infection. Objective. To study the role of Ang-2 in promoting vascular leakage in dengue viral infection. Methods. Prospective cohort study conducted at Prof. Dr. R.D. Kandou, Pancaran Kasih and R.W. Mongonsidi General Hospitals in Manado, from March 2013 to October 2014. Children, aged 1-15 years old, with the diagnosis of dengue viral infection according to 1997 World Health Organization (WHO) criteria [Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF), Dengue Shock Syndrome (DSS)],were recruited consecutively. Written informed consent was obtained from parents or legal guardian. Blood samples were obtained at the time of diagnosis and 48 hours after, evaluated for complete blood counts, albumin, NS-1, Ig M, Ig G anti-dengue, and Ang-2. Results. During the study period, there were 119 children with dengue viral infections (39 DF, 39 DHF, 41 DSS). Patient’s characteristics: female predominance, age between 1.5-8.5 years old, well nourished, and mean albumin level were less than ≤3.5 gr% in the DHF and DSS group. Ang-2 level at admission were 2,486.21 pg/dl, 3,194.95 pg/dl and 4,005.32 pg/dl in DF, DHF and DSS group, respectively. Anova test analyses shows significant differences in serum Ang-2 level at admission between DF, DHF and DSS group (p<0.0001). Between those groups, DSS group had the highest level of Ang-2, followed with DHF and DF. Discussion. Mean albumin level were 3.88 gr%, 3.39 gr% and 2.63gr% in DF, DHF and DSS group, respectively. This results shows increasing plasma leakage with increasing severity of dengue viral infection. Increasing level of Ang-2 can promote blood vessels instability therefore causing increased vascular permeability and subsequent plasma leakage. In this study, we found significant elevation of serum Ang-2 in patiens with DSS compared to DHF and DF but the difference was not significant between DF and DHF group. Conclusions. Angiopoietin-2 contributes in transient systemic vascular leak in dengue viral infection.

Tumor Necrosis Factor-Alpha and 8-Hydroxy-2'-Deoxyguanosine are Associated with Elevated Urinary Angiopoietin-2 Level in Type 2 Diabetic Patients with Albuminuria

Background/Aims: We previously showed that urine and serum Angiopoietin-2 (Ang-2) levels increased significantly with the degree of albuminuria in diabetes patients, but the reasons remain unclear. Consequently we aimed to determine whether there was an association between Ang-2, inflammatory cytokines (TNF-α and IL-18) and reactive oxygen species (8-OHdG and SOD) in type 2 diabetes patients with albuminuria. Methods: This retrospective study evaluated 113 patients with type 2 diabetes and normoalbuminuria, microalbuminuria, or macroalbuminuria and 30 healthy controls. Serum and urine TNF-α, IL-18 and 8-OHdG levels were measured by ELISA. Superoxide dismutase (SOD) activity was determined by spectrophotometry. Results: Serum and urine TNF-α, IL-18 and 8-OHdG levels increased significantly with the degree of albuminuria, and were positively correlated with increased Ang-2. In contrast, SOD activity decreased with the degree of albuminuria and was negatively correlated with Ang-2. Multivariable linear regression analysis revealed that serum Ang-2 level was independently associated with serum levels of TNF-α (P<0.001), 8-OHdG (P=0.001), and IL-18 (P=0.003). Urinary Ang-2 level was independently associated with urinary TNF-α (P<0.001) and 8-OHdG (P=0.004) levels. Conclusion: TNF-α and 8-OHdG are associated with elevated urinary Angiopoietin-2 levels in type 2 diabetic patients with albuminuria.

Serum Angiogenesis Markers and Their Correlation with Ultrasound-Detected Synovitis in Juvenile Idiopathic Arthritis.

Synovial angiogenesis is considered to be an important early step in the pathogenesis of juvenile idiopathic arthritis (JIA). In this study we assessed levels of angiogenic markers in serum or synovial fluid and their possible relevance to disease activity or degree of ultrasound signs of synovial inflammation and angiogenesis in early JIA. The concentration of vascular endothelial growth factor (VEGF), its soluble receptors 1 and 2 (sVEGF-R1, sVEGF-R2), and angiopoietins 1 and 2 (ANG-1, ANG-2) were evaluated in 43 JIA patients and 23 healthy controls. Synovial angiogenesis was assessed by means of Power-Doppler Ultrasonography (PDUS), according to the fourth-grade vascularity scale. VEGF and its receptors' (sVEGF-R1, sVEGF-R2) serum levels were significantly higher in JIA patients (p = 0.002). We found large variation in serum ANG-1 and ANG-2 levels. The PDUS imaging identified increased synovial microvascular blood flow in 15 (35.7%) examined JIA children. Intensity of joint vascularization correlated with higher serum VEGF and its levels was lowest in grade 0 and highest in grade 3 (p < 0.007 and p < 0.001, resp.). In conclusion, the high correlation between synovial microvascular blood flow, serum angiogenic proteins, and symptoms of synovitis may indicate its important role in pathogenesis of JIA.

Evaluation of angiopoietin 1 and 2, vascular endothelial growth factor, and tumor necrosis factor alpha levels in asthmatic children.

Asthma is characterized by chronic airway inflammation that is associated with structural changes termed airway remodeling. Recently, cytokines/mediators that augment inflammation have been attracting attention in this field. The aim of this study was to evaluate serum angiopoietin (Ang)-1, Ang-2, vascular endothelial growth factor (VEGF), and tumor necrosis factor (TNF) alpha values, which have important roles in inflammation, angiogenesis, and remodeling in asthmatic children. We also documented correlations between demographic features, duration of asthma, and pulmonary function test (PFT) parameters. Randomly selected 40 children (20 male and 20 female children, aged 6-16 years) with mild or moderate persistent asthma and 32 healthy children (15 male and 17 female children, aged 6-16 years) enrolled in the study. All asthmatic children had been using inhaled corticosteroids at least for the last 3 months. Serum Ang-1 levels were significantly lower in asthmatic children than those in normal controls. The Ang-1/Ang-2 ratio was also significantly lower in asthmatic children compared with those in normal controls (p < 0.01). However, serum Ang-2, VEGF, and TNF-alpha levels were similar in the two groups. A significant positive correlation was found between VEGF and duration of asthma. No correlation between serum Ang-1, Ang-2, VEGF values, and PFT parameters was obtained. On the other hand, significant negative correlation was detected between serum TNF-alpha and forced expiratory volume in 1 second. We have shown that serum Ang-1 levels and Ang-1/Ang-2 ratio were significantly reduced and balance was toward Ang-2 in asthmatics children. This process may lead to inflammation, destabilization of blood vessels, and trigger remodeling.

Angiopoietin-2 and angiopoietin-2/angiopoietin-1 ratio as indicators of potential severity of Plasmodium vivax malaria in patients with thrombocytopenia.

IntroductionAngiogenic factors such as angiopoietin 1 (Ang-1) and angiopoietin 2 (Ang-2) are biomarkers produced during activation and dysfunction of the vascular endothelium in several infectious diseases. The aim of this study was to determine the serum levels of Ang-1 and Ang-2 and to establish their relationship with the main indicators of worst-case prognosis in patients with P. vivax malaria.MethodsThis is a retrospective case-control study nested within a cohort of symptomatic malaria patients. A potentially severe case was defined as a patient that presented at least one of the main indicators of the worst-case prognosis for falciparum malaria, as established by the World Health Organization. Ang-2 and Ang-1 and the Ang-2/Ang-1 ratio were used to analyze the role of angiopoietins as biomarkers in signaling potentially severe vivax malaria. ROC curves were generated to identify a cut-off point discriminating between the angiopoietin concentrations that were most strongly associated with potential infection severity.ResultsThe serum levels of Ang-2 and the Ang-2/Ang-1 ratio were higher in the case group. In contrast, the serum levels of Ang-1 were lower in the cases than in the control patients. The blood count for platelets showed a positive correlation with Ang-1 and a negative correlation with Ang-2 and with the Ang-2/Ang-1 ratio. The area under the ROC curve (AUC) for serum angiopoietins, as an indicator of worst-case prognosis in a potentially severe P. vivax malarial infection, was larger in the subgroup of patients with platelet counts <75,000/µL.ConclusionThis study showed that patients with predictors of worst-case prognoses for P. vivax malaria have lower Ang-1 and higher Ang-2 serum levels (and higher values for the Ang-2/Ang-1 ratio) than controls. Elevated serum levels of Ang-2 and high values for the Ang-2/Ang-1 ratio may potentially be used as predictors of worst-case prognoses for P. vivax malaria, especially in patients with thrombocytopenia.

Serum angiopoietin-2 and soluble VEGFR-2 levels predict malignancy of ovarian neoplasm and poor prognosis in epithelial ovarian cancer.

BackgroundThe aim of the study was to explore the serum levels of eight angiogenesis biomarkers in patients with benign, borderline or malignant epithelial ovarian neoplasms and to compare them to those of healthy controls. In addition, we aimed to study how those biomarkers predict the clinical course and survival of patients with epithelial ovarian cancer.MethodsWe enrolled 132 patients with ovarian neoplasms and 32 unaffected women in this study. Serum samples were collected preoperatively at the time of diagnosis and the levels of angiogenesis biomarkers were measured with an ELISA.ResultsLevels of Ang-1, Ang-2, VEGF, VEGF-D, VEGF/sVEGFR-2 and Ang-2/ sVEGFR-2 ratios were elevated whereas sVEGFR-2 was lower in patients with ovarian carcinoma than in women with normal ovaries, benign and/or borderline ovarian neoplasms. In ROC analysis, the area under the curve for serum Ang-2/sVEGFR-2 ratio (0.76) was greater than Ang-2 (0.75) and VEGF (0.65) but lower than for CA 125 (0.90) to differentiate ovarian cancer from benign or borderline ovarian tumors. In ovarian cancer high Ang-2/sVEGFR-2 ratio was associated with the presence of ascites, high stage and grade of ovarian cancer, with the size of primary residual tumor >1 cm and with recurrence of disease. Elevated Ang-2, VEGF, VEGF/sVEGFR-2, Ang-2/VEGF and Ang-2/sVEGFR-2 ratios and low level of sVEGFR-2 were significant predictors of poor overall survival (OS) and recurrence free survival (RFS) in univariate survival analyses.ConclusionsOvarian cancer patients had elevated levels of angiogenesis related growth factors in circulation reflecting increased angiogenesis and poor prognosis. The serum level of Ang-2 predicted most accurately poor OS and Ang-2/sVEGFR-2 ratio malignancy of ovarian neoplasms and short RFS.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-696) contains supplementary material, which is available to authorized users.

Serum angiopoietin is associated with lung function in patients with asthma: a retrospective cohort study.

BackgroundAngiopoietin-1 (Ang-1) is an essential mediator of angiogenesis that establishes vascular integrity, and angiopoietin-2 (Ang-2) acts as its natural inhibitor. We considered that angiopoietin might be important in bronchial asthma.MethodsIn total, 35 patients with asthma and 20 healthy subjects were studied.ResultsThe serum Ang-1 levels were significantly elevated in patients with asthma compared to control subjects (293.9 ± 13.8 pg/mL vs. 248.3 ± 16.2 pg/mL, respectively, p = 0.04). The serum Ang-2 levels were not different between the two groups. The areas under the curve (AUC) for serum angiopoietins revealed that the serum level of Ang-1 (0.68) was more sensitive and specific than the serum Ang-2 level (0.55) for differentiating between patients with asthma and control subjects. The serum Ang-1/Ang-2 ratio was correlated with the FEV1/FVC ratio (r = -0.312, p = 0.02), while serum Ang-2 was correlated with body mass index.ConclusionsOur results indicate that the serum Ang-1 levels were higher in asthma patients compared with healthy subjects. As the Ang-1/Ang-2 ratio was related to lung function, the data suggest that serum angiopoietin is associated with lung function in patients with asthma.

Effects of laser photocoagulation on serum angiopoietin-1, angiopoietin-2, angiopoietin-1/angiopoietin-2 ratio, and soluble angiopoietin receptor Tie-2 levels in type 2 diabetic patients with proliferative diabetic retinopathy.

To determine the effects of laser photocoagulation on serum levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), soluble angiopoietin receptor Tie-2 (Tie-2), Ang-1/Ang-2 ratio and vascular endothelial growth factor (VEGF) in patients with type 2 diabetes mellitus (T2DM) and proliferative diabetic retinopathy (PDR). We also explored the role of the Ang/Tie system in PDR. 160 patients with T2DM, including 50 patients with non-diabetic retinopathy (NDR), 58 patients with non-proliferative diabetic retinopathy (NPDR), and 52 patients with PDR were enrolled in this study. Serum Ang-1, Ang-2, Tie-2 receptor and VEGF levels were measured using enzyme-linked immunosorbent assays for all patients and were repeated in 26 patients who underwent laser photocoagulation two months after the procedure. The median levels of Ang-2 and VEGF in serum were significantly higher in the NPDR group (4.23 ng/mL and 303.2 pg/mL, respectively) compared to the NDR group (2.67 ng/mL and 159.8 pg/mL, respectively, P<0.01), with the highest level in the PDR group (6.26 ng/mL and 531.2 pg/mL, respectively, P<0.01). The median level of Ang-1 was significantly higher in the NPDR group (10.77 ng/mL) compared to the NDR group (9.31 ng/mL) and the PDR groups (9.54 ng/mL) (P<0.05), while no difference was observed between the PDR and NDR groups. Ang-1/Ang-2 ratio of PDR group was lowest in three groups (1.49 vs 2.69 and 2.90, both P<0.01). The median level of Tie-2 was not significantly different among three groups (P>0.05). Ang-2 was positively correlated with VEGF and Tie-2 in the PDR and NPDR groups (both P<0.05). Among the 26 patients who underwent laser photocoagulation, serum Ang-2 and VEGF levels significantly decreased (both P<0.05), whereas serum Ang-1 level and Ang-1/Ang-2 ratio were weakly increased (P>0.05). The median levels of Ang-2 and VEGF in serum were highest in PDR group, however, Ang-1/Ang-2 ratio of PDR group was lowest in three groups. Laser photocoagulation can reduce serum Ang-2 and VEGF levels. The Ang/Tie system and VEGF play an important role in the development and progression of T2DM patients with PDR.

Prognostic impact of angiopoietin-2 in multiple myeloma.

Angiogenesis is an essential process for the expansion of multiple myeloma (MM). Angiopoietin-2 (Ang-2), Ang-1 and their receptor possess important roles in this procedure. The aim of the study was to measure serum levels of Ang-2 along with known markers of angiogenesis and to estimate their prognostic impact on the survival. Bone marrow microvascular density (MVD), estimated by CD31, and circulating levels of known angiogenic factors Ang-2, interleukin-6, soluble CD105 and platelet-derived growth factor-AB, measured by ELISA, were measured in 77 newly diagnosed patients with active MM and in 57 of them who responded to chemotherapy. All measured parameters were increased in MM patients, were also increasing in advanced disease and decreased after effective treatment. Ang-2 correlated positively with the other angiogenic factors and MVD. Moreover, Ang-2 values above the median were accompanied by worse survival. Ang-2 correlates strongly with the angiogenic process and its serum levels are importantly prognostic for survival, highlighting the role of angiopoietins pathway in the biology of MM.

PTH-138 Tnf-a Dependent Angiopoeitin Mediated Angiogenesis In Sporadic Small Bowel Angiodysplasia; Novel Pathophysiology And Potential Clinical Marker

IntroductionAngiodysplasias account for over 50% of small bowel causes of obscure gastrointestinal bleeding. Angiodysplasias are thought to develop as a result of an imbalance in the angiogenic cascade, although the...

THU0557 Nailfold Videocapillaroscopic Abnormalities and Selected Angiogenesis Modulators in Patients with Raynaud's Phenomenon after Multiwave Locked System (MLS) Laser Therapy

BackgroundRaynaud's phenomenon (RP) is a vascular disorder characterised by reversible vasospastic response of the fingers and toes to cold or emotional stimuli. It can be primary (idiopathic) or secondary (Raynaud's...

Disturbed Balance between Serum Levels of Receptor Tyrosine Kinases Tie-1, Tie-2 and Angiopoietins in Systemic Sclerosis

Objective: The aim of this study was to determine the characteristic factors for vascular development and maintenance levels as well as correlation between Tie-1 receptors, Tie-2 receptors and the corresponding ligands - angiopoietins - in systemic sclerosis (SSc) patients. Materials and Methods: Serum levels of Tie-1, Tie-2, Ang-1 and Ang-2 were measured in 25 SSc patients and healthy controls. Results: There was a statistically significant difference in serum Tie-1 (p = 0.009) and Ang-2 (p = 0.001) levels in SSc patients compared with healthy controls. Significant correlations between Tie-1 and Tie-2 (ρ = 0.70, p = 0.0001) and between Tie-1 and Ang-2 (ρ = -0.92, p = 0.002) were found in the SSc group. Serum levels of Tie-2 were positively associated with esophagus changes (U = 2.03, p = 0.041) and Ang-1 was negatively correlated with duration of Raynaud's phenomenon (ρ = -0.75, p = 0.00008). Conclusion: The increase in serum concentration of Tie-1 and Ang-2 in patients with SSc may confirm a molecular imbalance between receptor tyrosine kinases Tie and their ligands.

Serum Levels of Angiopoietin-2, but not Angiopoietin-1, are Elevated in Patients with Erythrodermic Cutaneous T-cell Lymphoma

Angiogenesis is a crucial process in the growth and progression of cancer, correlating with the metastatic potential of tumour cells. Angiopoietins are ligands for the endothelium-specific tyrosine kinase Tie2 receptor, which comprise 4 structurally related proteins, termed angiopoietin (Ang)-1, Ang-2, Ang-3 and Ang-4. The roles of Ang-1 and Ang-2 have recently been clarified as crucial in angiogenesis. In this report, we measured serum Ang-1 and Ang-2 levels in patients with cutaneous T-cell lymphoma (CTCL). Serum levels of Ang-2, but not Ang-1, in patients with Sézary syndrome were significantly higher than those in patch mycosis fungoides (MF), plaque/tumour MF, and healthy controls. In patients with CTCL, serum Ang-2 correlated with disease activity. Moreover, the numbers of Ang-2+ cells in lesional skin of CTCL were significantly larger than those in normal skin. These results suggest that Ang-2 may have important roles in the development of CTCL.

Local Synovial Engagement of Angiogenic TIE‐2 Is Associated With the Development of Persistent Erosive Rheumatoid Arthritis in Patients With Early Arthritis

To examine the role of vascular endothelial growth factor (VEGF) and angiopoietin signaling in the diagnosis and disease outcome of patients with early arthritis. Fifty patients with early arthritis (disease duration <1 year) who had not been treated with disease-modifying antirheumatic drugs (DMARDs) were monitored prospectively and were classified at baseline and after 2 years as having undifferentiated arthritis (UA), rheumatoid arthritis (RA), or spondyloarthritis (SpA). All patients underwent arthroscopic synovial biopsy at baseline. Synovial expression of VEGF, VEGF receptor, angiopoietin 1 (Ang-1), Ang-2, TIE-2, and activated p-TIE-2 was evaluated by immunohistochemistry. Serum levels of VEGF, Ang-1, and Ang-2 were measured by enzyme-linked immunosorbent assay. Secreted products of macrophages stimulated with Ang-1 and Ang-2 were measured using a multiplex system. Expression of Ang-1 was comparable between the patients with RA at baseline and patients with UA who fulfilled the criteria for RA over time (UA/RA), and it was significantly higher in patients with RA (P < 0.05) or UA/RA (P < 0.005) than in patients with SpA. TIE-2 and p-TIE-2 were more highly expressed in patients with RA (P < 0.005) or UA/RA (P < 0.05) than in patients with SpA. Ang-1 significantly enhanced the tumor necrosis factor-dependent macrophage production of cytokines and chemokines that are known to be elevated in the synovial fluid of patients with early RA. In RA, relative TIE-2 activation predicted the development of erosive disease (R(2) = 0.35, P < 0.05). Local engagement of synovial TIE-2 is observed during the earliest phases of RA, suggesting that TIE-2 signaling may contribute to disease development and progression or may indicate an attempt to protect against these processes. Early therapeutic targeting of TIE-2 signaling may be useful in improving outcome in arthritis.

Angiopoietin 1 and 2 serum concentrations in first trimester of pregnancy as biomarkers of adverse pregnancy outcomes

To assess angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and the Ang-1/Ang-2 ratio levels in the first trimester of pregnancy, their association with adverse pregnancy outcomes, and their predictive accuracy. This cohort study measured serum Ang-1 and Ang-2 levels in 4785 women with singleton pregnancies attending first trimester screening in New South Wales, Australia. Multivariate logistic regression models were used to assess the association and predictive accuracy of serum biomarkers with subsequent adverse pregnancy outcomes (small for gestational age, preterm birth, preeclampsia, miscarriage >10 weeks, and stillbirth). Median (interquartile range) levels for Ang-1, Ang-2, and the Ang-1/Ang-2 ratio for the total population were 19.6 ng/mL (13.6-26.4), 15.5 ng/mL (10.3-22.7), and 1.21 (0.83-1.73), respectively. Maternal age, weight, country of birth, and socioeconomic status significantly affected Ang-1, Ang-2, and the Ang-1/Ang-2 ratio levels. After adjusting for maternal and clinical risk factors, women with low Ang-2 levels (<10th percentile) and high Ang-1/Ang-2 ratio (>90th percentile) had increased risk of developing most adverse pregnancy outcomes. Compared with the Ang-1/Ang-2 ratio alone, maternal and clinical risk factors had better predictive accuracy for most adverse pregnancy outcomes. The exception was miscarriage (Ang-1/Ang-2 ratio area under receiver operating characteristic curve = 0.70; maternal risk factors = 0.58). Overall, adding the Ang-1/Ang-2 ratio to maternal risk factors did not improve the ability of the models to predict adverse pregnancy outcomes. Our findings suggest that the Ang-1/Ang-2 ratio in first trimester is associated with most adverse pregnancy outcomes, but do not predict outcomes any better than clinical and maternal risk factor information.

Serum Angiopoietin-2 and CRP Levels During COPD Exacerbations

Background and Objective: Angiopoietin-2 (Ang-2) is an important mediator of angiogenesis and has been implicated in many inflammatory diseases. COPD is characterized by systemic inflammation, which is enhanced during exacerbations and may be assessed by measuring serum C-reactive protein (CRP). The aim of the study was to evaluate serum CRP and Ang-2 levels on the first (D1) and seventh day (D7) of hospitalization due to a COPD exacerbation and to examine possible associations of CRP and Ang-2 levels and kinetics with the length of hospital stay and outcome. Methods: We conducted a prospective study and evaluated 90 patients admitted to the hospital with a diagnosis of an acute exacerbation of COPD. A venous blood sample was obtained from all patients on D1 and D7 of hospitalization, for the measurement of Ang-2 and CRP. Results: Serum Ang-2 levels were significantly higher on D1 compared to D7 during the course of COPD exacerbation (p < 0.001). Serum CRP levels were also significantly higher on D1 compared to D7 (p < 0.001). Serum Ang-2 presented a significant positive correlation with CRP levels both on D1 and D7 (r = 0.315 and r = 0.228, respectively). Patients with unfavorable outcome had significantly higher Ang-2 levels both on D1 (p = 0.04) and D7 (p = 0.01). Conclusions: Serum Ang-2 levels are elevated at the onset of COPD exacerbations and are positively associated with CRP levels. Ang-2 levels decrease during the course of COPD exacerbations in patients with favorable outcome. Serum Ang-2 may serve as a biomarker that could predict the outcome of a COPD exacerbation.

Significance of serum levels of angiopoietin-2 and its relationship to Doppler ultrasonographic findings in rheumatoid arthritis patients

BackgroundAngiopoietin-2 (Ang-2) is connected to angiogenesis in synovial regions, but the significance of its levels in patients with rheumatoid arthritis (RA) is still unclear. Aim of the workTo evaluate the significance of serum levels of Ang-2 in patients with RA. Also, to determine Ang-2 relationship to the findings of joints Doppler ultrasonographic findings. Patients and methodsThis study included 40 patients with RA, and 25 matched healthy controls. All patients were subjected to assessment of pain using visual analogue scale (VAS), assessment of personal activity using the Health Assessment Questionnaire (HAQ) score, and calculation of disease activity score (DAS 28). Laboratory assays of complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) titre, and measurement of serum levels of Ang-2 by ELISA. Doppler ultrasonography (US) assessment for eight joints, with calculation of synovial thickness and total signal score (TSS), was done. ResultsSerum Ang-2 levels were significantly higher among patients (3191.3±594.9pg/ml) than controls (1771.7±103.1pg/ml) (p<0.001). Serum Ang-2 levels were significantly correlated with ESR, CRP, DAS28, and duration of morning stiffness (p<0.001, p<0.001, p<0.001, and p=0.025, respectively). There was a significant correlation between serum Ang-2 levels and findings of US, regarding joint synovial thickness, and TSS (p<0.001, for both). ConclusionPatients with RA had significantly higher levels of serum Ang-2 versus controls. In those patients, serum Ang-2 levels were significantly correlated with disease activity markers (ESR, CRP), DAS28, and duration of morning stiffness. Moreover, these levels were significantly correlated with synovial thickness, and TSS. The role of Ang-2 in RA pathogenesis might open the door to the development of new therapeutic strategies, particularly which target angiogenesis.