Serum Concentrations Of Ang-2 Research Articles

Myxomatous mitral valve disease and associated pulmonary hypertension might increase serum angiopoietin-2 in dogs.

To evaluate the relationships between the severity of myxomatous mitral valve disease (MMVD) and pulmonary hypertension (PH) and serum angiopoietin (Ang)-1 and Ang-2 concentrations in dogs with MMVD. 74 dogs (control, n = 12; MMVD, n = 62) were included. Serum Ang-1 and Ang-2 concentrations were estimated using the canine-specific ELISA kit. The concentrations were compared between dogs with MMVD and healthy dogs, and they were analyzed according to the severity of MMVD and PH. The median serum Ang-1 concentration did not differ among the study groups. The median serum Ang-2 concentration was higher in dogs with stage B2 MMVD (P = .041) and acute congestive heart failure (P = .002) than in control dogs. In addition, the median serum Ang-2 concentration was higher in MMVD dogs with PH than in those without PH (P = .031). Serum Ang-2 concentration was correlated with vertebral heart score (rs = 0.36, P = .004) and vertebral left atrial score (r = 0.50, P < .001) in dogs with MMVD, and correlated with vertebral heart score (r = 0.63, P = .01), maximum E wave amplitude of the diastolic transmitral flow (rs = 0.61, P = .018), ejection fraction (rs = -0.77, P < .001) and fractional shortening (rs = -0.56, P = .032) in dogs with acute congestive heart failure. Circulating Ang-2 levels increase in dogs with the severity of MMVD and the presence of PH.

Biomarkers of endothelial dysfunction and atherosclerosis in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with an increased prevalence of subclinical atherosclerosis and cardiovascular risk. Angiopoietin-2 (Ang-2), asymmetric dimethylarginine (ADMA), and osteoprotegerin (OPG) are molecules related to endothelial dysfunction (ED) and atherosclerosis, but also to disease severity in patients with chronic inflammatory disorders. In this case-control study, we aimed to investigate serum Ang-2, ADMA, and OPG levels in patients with HS, and to assess the potential relationship between these levels and disease severity. Seventy-five patients with HS and 60 controls were assessed. Serum Ang-2, ADMA, and OPG concentrations were determined in all participants. HS patients had significantly higher Ang-2 and ADMA levels than controls after adjusting for confounders. Besides, Ang-2 concentrations positively correlated with disease severity in the adjusted multivariable analysis. Nevertheless, serum OPG levels did not significantly differ between HS patients and controls. Our results indicate that serum Ang-2 and ADMA levels are significantly increased in patients with HS. Furthermore, Ang-2 might be a suitable marker of HS severity.

Angiopoietin-2 predicts all-cause mortality in male but not female end-stage kidney disease patients on hemodialysis.

ABSTRACTBackgroundAngiopoietin-2 (Ang-2) plays a pivotal role in pathological vascular remodeling and angiogenesis. Both vascular mechanisms are active in patients with end-stage renal disease (ESRD) and may contribute to the high mortality in these patients. The aim of this multicenter prospective cohort study was to investigate baseline serum Ang-2 concentrations in ESRD patients on hemodialysis (HD) for their ability to predict all-cause mortality.MethodsWe conducted a prospective cohort study in 340 stable HD patients from different chronic dialysis centers in Berlin, Germany. The primary endpoint was all-cause mortality during a 5-year follow-up period. Blood samples and clinical data were collected at baseline. Serum Ang-2 was measured with a validated enzyme-linked immunosorbent assay (Biomedica, Vienna, Austria).ResultsA total of 313 HD patients (206 men and 107 women) were finally included in the study. Receiver operating characteristic (ROC) analysis of Ang-2 concentrations yielded an area under the curve (AUC) of 0.65 (P < 0.0001) for predicting all-cause mortality in the entire study population and was used to determine the optimal cut-off (111.0 pmol/L) for all-cause mortality. Kaplan–Meier survival analysis indicated that male but not female end-stage kidney disease patients on HD with higher Ang-2 concentrations had a significantly lower survival (log-rank test, P < 0.0001 and P = 0.380 for male and female patients, respectively). Multivariable Cox regression analyses adjusted for age, comorbidity, smoking, dialysis vintage, serum creatinine, hemoglobin, C-reactive protein, serum albumin, intact parathyroid hormone (iPTH), low-density lipoprotein (LDL) and Kt/V likewise indicated that elevated Ang-2 concentrations are associated with all-cause mortality in male {hazard ratio [HR] 3.294 [95% confidence interval (CI) 1.768–6.138]; P = 0.0002} but not in female end-stage kidney disease patients on HD [HR 1.084 (95% CI 0.476–2.467); P = 0.847].ConclusionAng-2 at baseline is independently associated with all-cause mortality in male ESRD patients on HD.

The role of angiopoietin-2 and surfactant protein-D levels in SARS-CoV-2-related lung injury: A prospective, observational, cohort study.

IntroductionCoronavirus disease‐2019 (COVID‐19) is a respiratory disease whose clinical manifestation ranges from asymptomatic to severe respiratory failure. The purpose of this study was to investigate the place of serum surfactant‐D (SP‐D) and angiopoetin‐2 (Ang‐2) levels in predicting severity of disease in patients diagnosed with COVID‐19.MethodsSixty‐four patients diagnosed with COVID‐19 between September 2020 and February 2021, 50 patients diagnosed with community‐acquired pneumonia and a 50‐member healthy control group were included in the study. Plasma samples and clinical data were collected within 72 h after admission, during hospital stay. Serum SP‐D and Ang‐2 concentrations were measured using the enzyme‐linked immunosorbent assay.ResultsSP‐D and Ang‐2 levels were significantly higher in the mild–moderate pneumonia and severe/critical patient groups compared to the asymptomatic and noncomplicated COVID‐19 patients (p < 0.001 for all groups). Serum SP‐D and Ang‐2 levels of severe‐critical COVID‐19 patients were significantly higher than CAP patients (p < 0.001). Powerful correlation was present between clinical severity of COVID‐19 and SP‐D and Ang‐2 levels (r = 0.885 p < 0.001 and r = 0.913 p < 0.001, respectively). Cut‐off values of 37.7 ng/ml (AUC = 0.763, p < 0.001, 95% confidence interval [CI] = 0.667–0.860) for SP‐D and 4208.3 pg/ml (AUC = 0.659, p = 0.004, 95% CI = 0.554–0.763) for Ang‐2 were identified as predictors of COVID‐19 disease at receiver operating characteristic curve analysis.ConclusionSP‐D and Ang‐2 are predictive factors in differentiating COVID‐19 patients and determining severity of disease. These data may be important for the initiation of treatment in the early stage of the disease in patients with COVID‐19.

Serum Angiopoietin-1 and -2 and VEGF are associated with severe disease in vivax malaria.

Malaria continues to be a significant public health problem in tropical countries including India; however, there are limited tools to predict occurrence of severe disease due to malaria. This study was designed to evaluate the role of Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Vascular endothelial growth factor (VEGF) and Asymmetric Dimethylarginine (ADMA)as disease biomarkers in uncomplicated malaria (UM) and severe malaria (SM). This is a prospective observational study carried out at All India Institute of Medical Sciences (AIIMS), tertiary referral hospital in New Delhi, India. The study population included patients diagnosed with malaria (Plasmodium falciparum or Plasmodium vivax) either by rapid diagnostic kit test or positive peripheral smear and age more than 12 years. Forty-nine patients (25 with SM, 24 with UM) and 22 controls were recruited. In addition to routine investigations, serum concentrations of Ang-1, Ang-2, VEGF and ADMA were measured using ELISA technique. We observed Ang-1 serum levels to be significantly lower in patients with severe malaria (7775 pg/ml) compared to uncomplicated malaria (17629 pg/ml) and healthy controls (43472 pg/ml) [p <0.001]. Ang-2 levels were significantly higher in severe malaria (11100 pg/ml) compared to uncomplicated malaria (7315 pg/ml) and healthy controls (3679 pg/ml) (p <0.001). The ratio of Ang-2/Ang-1 was significantly higher in patients with severe malaria. VEGF serum levels was significantly lower in severe malaria (130.36 pg/ml) compared to uncomplicated malaria (317.3 pg/ml). The Ang-1, Ang-2 and VEGF levels were able to differentiate severe malaria from uncomplicated malaria caused by P. vivax but not with P. falciparum. We conclude that Ang-1, Ang-2 and VEGF are markers of disease severity in vivax malaria.

Circulating Vascular Growth Factors and Magnetic Resonance Imaging Markers of Small Vessel Disease and Atrophy in Middle-Aged Adults.

Background and Purpose- Little is known about associations between vascular growth factors and magnetic resonance imaging (MRI) markers in midlife. We investigated the association of serum VEGF (vascular endothelial growth factor), Ang2 (angiopoietin 2), sTie2 (soluble tyrosine kinase with immunoglobulin-like and EGF-like domains 2), and HGF (hepatocyte growth factor) concentrations with MRI markers of brain aging in middle-aged adults. Methods- We evaluated 1853 participants (mean age, 46±9 years; 46% men) from the Framingham Heart Study. Serum growth factor concentrations were measured using standardized immunoassays. Outcomes included total brain, cortical and subcortical gray matter, white matter, cerebrospinal fluid, and white matter hyperintensity volumes derived from MRI; as well as fractional anisotropy in white matter tracts from diffusion tensor imaging. We related VEGF, Ang2, sTie2, and HGF to MRI measures using multivariable regression models adjusting for vascular risk factors. We tested for interactions with APOE (apolipoprotein E) genotype and CRP (C-reactive protein). Results were corrected for multiple comparisons. Results- Higher sTie2 was associated with smaller total brain (estimate by SD unit±SE=-0.08±0.02, P=0.002) and larger white matter hyperintensity (0.08±0.02, P=0.002) volumes. Furthermore, higher Ang2 (0.06±0.02, P=0.049) and HGF (0.09±0.02, P=0.001) were associated with larger cerebrospinal fluid volumes. Finally, higher Ang2 was associated with decreased fractional anisotropy, in APOE-ε4 carriers only. Conclusions- Vascular growth factors are associated with early MRI markers of small vessel disease and neurodegeneration in middle-aged adults.

Serum Angiopoietin-2 levels as a marker in type 2 diabetes mellitus complications

Angiopoietin-2 (Ang-2) has been reported to be involved in the development of type 2 diabetes (T2D) and accelerates micro and macro vascular complication. The current study aimed to investigate serum Ang-2 levels in Saudi patients with type 2 diabetes and its complications. In this observational cross-sectional study, serum was collected from 329 T2D subjects aged 34–79 years. All subjects were evaluated for fasting blood glucose (FBG), HbA1c, lipid profile, and kidney profile. Serum concentration of Ang-2 was assayed by ELISA-based method. Mean serum Ang-2 level was significantly higher in female T2D subjects (2881 ± 1550 pg/ml) compared with male T2D subjects (2450 ± 1477 pg/ml). The mean serum Ang-2 levels in female T2D subjects significantly increased with increase in their age and BMI, while mean serum Ang-2 levels did not significantly increase among the male with their age and BMI. A significantly higher level of Ang-2 was found in patients with diabetic complications like neuropathy (3293 ± 1728 pg/ml), retinopathy (2986 ± 1645 pg/ml), and vascular complications (3152 ± 1571 pg/ml). The study has established comprehensive Ang-2 levels in various subsets of adults with diabetes. While interpreting Ang-2 levels, the differences in age and sex need to be taken into account. Diabetic patients with higher Ang-2 levels should be monitored closely and level of serum Ang-2 should be served as a marker to identify patients at high risk of diabetic complications.

Angiopoietin-2 (Ang-2) is a useful serum tumor marker for liver cancer in the Chinese population

BackgroundWe estimated the diagnostic and prognostic value of serum angiopoietin-2 (Ang-2) in liver cancer patients. MethodsTissue Ang-2 was measured using immunohistochemistry (IHC). Cell localization of Ang-2 was tested using immunofluorescence (IF). Cell viability and apoptosis were evaluated using MTT and caspase3/7 assays, respectively. Colony-formation was measured using a soft agar assay. Serum Ang-2 was examined using enzyme-linked immunosorbent assay (ELISA) and Western blotting. ResultsAng-2 was up-regulated in liver cancer compared to the levels in normal tissues. Serum Ang-2 concentrations were much higher in liver cancer patients than in healthy individuals and those with chronic liver disease (CLD). Inhibitions of Ang-2 using specific shRNA decreased cell proliferation. Serum Ang-2 decreased significantly after surgery. Serum Ang-2 was positively correlated with serum alpha-fetoprotein (AFP; R=0.375, P=0.005). Receiver operating characteristic (ROC) curves suggested that serum Ang-2 could be used with relatively high sensitivity and specificity in differentiating liver cancer patients from CLD patients or healthy controls, with corresponding AUC values of 0.742 and 0.924, respectively. Serum Ang-2 was negatively correlated with overall survival. Subgroup analysis also showed that Ang-2 retained its prognostic value in overall survival prediction in different risk subgroups. ConclusionSerum Ang-2 may be a useful tumor marker in predicting liver cancer prognosis.

Serum concentrations of Ang-2 and Flt-1 may be predictive of pregnancy outcome in women with pregnancies of uncertain viability: a phase I exploratory prognostic factor study

The aim of this study was to determine whether serum concentrations of Ang-1, Ang-2, Flt-1, IL-15 and/or TRAIL can be used to predict outcome in women with pregnancies of uncertain viability (PUVs). Women presenting to the Early Pregnancy Unit at the Queen’s Medical Centre in Nottingham between 17.06.14 and 01.09.15 were prospectively recruited. Serum concentrations of Ang-1, Ang-2, Flt-1, IL-15 and TRAIL were measured in women with PUVs. Women were followed-up according to departmental protocols until viability was determined. Biomarker concentrations were correlated with pregnancy outcome. Ninety-four PUVs were studied, of which 61 (64.9%) were subsequently proven to be viable. There were statistically significant (p < .01), linear (p-valuetrend <.01) associations between Ang-2 and Flt-1 concentrations and pregnancy viability such that women with lower concentrations were significantly more likely to have viable pregnancies than women with higher concentrations. In conclusion, Ang-2 and Flt-1 may be useful in predicting outcome in women with PUVs.Impact statementWhat is already known on this subject: Predicting outcome in women with pregnancies of uncertain viability (PUVs) is challenging. There is currently no accurate and reliable method. All PUVs need to be followed-up until a definitive diagnosis of either a viable or non-viable pregnancy can be made. This takes time, utilises limited resources and generates significant anxiety. Recent studies have demonstrated serum concentrations of Ang-1, Ang-2, Flt-1, IL-15 and TRAIL in viable pregnancies are significantly different to those in non-viable or ectopic pregnancies.What the results of this study add: The results from this prospective study of 94 women with PUVs suggest that serum concentrations of Ang-2 and Flt-1 may be able to predict pregnancy viability in cases of uncertainty. Women with PUVs and low concentrations of Ang-2 or Flt-1 are significantly more likely to have viable pregnancies than women with high concentrations.What the implications are of these findings for clinical practice and/or further research: Evidence from multiple studies is necessary to appreciate the discriminating ability of these prognostic factors. Rapid clinical adoption in the absence of such evidence may lead to wasted resources. If our findings are confirmed, however, these biomarkers, either alone or as part of a prognostic model, may be capable of accurately predicting pregnancy outcome in cases of uncertainty. This would reduce the strain on limited resources and alleviate anxiety for women.

Circulating Angiopoietin-2 and Its Soluble Receptor Tie-2 Concentrations Are Related to Renal Function in Two Population-Based Cohorts.

BackgroundAn intact angiopoietin/Tie-2 ligand receptor system is indispensable for life. High circulating angiopoietin-2 (Ang-2) concentrations are strongly associated with kidney disease involving the progressive loss of glomerular filtration. The aim of our study was to investigate the associations between renal function and serum Ang-2 or serum Tie-2 concentrations in the general population.MethodsData of 3081 and 4088 subjects from two population-based studies, the Study of Health in Pomerania (SHIP-1) and SHIP-Trend, were used. Renal function was assessed by serum creatinine, cystatin C concentration, creatinine-based estimated glomerular filtration rate [eGFR(crea)], cystatin C-based eGFR [eGFR(cys)] and urinary albumin-to-creatinine ratio (uACR). Analyses of variance and linear regression models were calculated.ResultsIn both cohorts, strong positive associations between serum cystatin C concentrations and serum Ang-2 or Tie-2 concentrations as well as inverse associations between eGFR(cys) and serum Ang-2 or Tie-2 concentrations were found. These relations were also present in a subpopulation without hypertension or diabetes mellitus type 2. Furthermore, we detected weak U-shaped associations between serum creatinine concentrations or eGFR(crea) and serum Ang-2 concentrations. With respect to uACR a strong positive association with serum Ang-2 concentrations was revealed.ConclusionSerum Ang-2 concentrations are strongly associated with sensitive parameters of renal impairment like serum cystatin C, uACR and eGFR(cys). These findings persisted even after exclusion of subjects with hypertension or diabetes mellitus type 2, conditions that predispose to chronic renal disease and are associated with increased Ang-2 concentrations. Interestingly, we did not detect the same strong relations between serum creatinine and eGFR(crea) with serum Ang-2 concentration. Additionally, significant association of serum Tie-2 concentrations with cystatin C and eGFR(cys) were detected.

Effects of Percutaneous Coronary Intervention on Serum Angiopoietin-2 in Patients with Coronary Heart Disease.

Background:Angiopoietin-2 (Ang-2) plays a crucial role in hypoxia-induced angiogenesis and is expressed only in sites of vascular remodeling. Ang-2 expression can be regulated by hypoxia inducible factors and other regulators with exposure to hypoxia. The objective of this study was to investigate the influence of percutaneous coronary intervention (PCI) on serum Ang-2 concentrations, and analyze the correlation between serum Ang-2 and the severity of coronary artery stenosis in patients with coronary heart disease (CHD).Methods:Sixty-four patients with CHD were selected as the study group, each undergone PCI. Thirty-two healthy subjects were selected as the control group. Pre-PCI and post-PCI serum Ang-2 were measured by enzyme-linked immunosorbent assay. The severity of coronary artery stenosis was evaluated using angiographic Gensini scores, and the coronary collateral vessels were scored according to Rentrop's classification.Results:Concentrations of pre-PCI serum Ang-2 in the study group were significantly higher than those in the control group (4625.06 ± 1838.06 vs. 1945.74 ± 1588.17 pg/ml, P < 0.01); however, concentrations of post-PCI serum Ang-2 were significantly lower than those of pre-PCI (3042.63 ± 1845.33 pg/ml vs. 4625.06 ± 1838.06 pg/ml, P < 0.01). Concentrations of pre-PCI serum Ang-2 were significantly correlated with Gensini scores (r = 0.488, P < 0.01); however, the decrease in serum Ang-2 after PCI was not correlated with Gensini scores, coronary collateral vessel grading, or left ventricular ejection fraction.Conclusions:Serum Ang-2 concentrations significantly increased in patients with CHD, and PCI treatment significantly decreased these concentrations. Serum Ang-2 concentrations, but not the decrease in serum Ang-2 concentrations, were significantly correlated with the severity of coronary artery stenosis. These results suggested that Ang-2 may be a biomarker of myocardial ischemia and vessel remodeling.

Impact of angiopoietin-1 and -2 on clinical course of idiopathic pulmonary fibrosis

BackgroundAngiopoietin (Ang) -1 and -2 are glycoproteins that play roles in vascular development, angiogenesis, and lung vascular permeability. Although the serum concentrations of Ang-1 and -2 have been evaluated in patients with sepsis, those in patients with idiopathic pulmonary fibrosis (IPF) have received less attention. ObjectiveTo elucidate the clinical significance of Ang-1 and -2 in patients with IPF. MethodsSeventy-five patients with IPF were retrospectively studied. Serum concentrations of Ang-1 and -2 at diagnosis of IPF were measured by enzyme-linked immunosorbent assay. The relationships of the Ang-1 and -2 concentrations with pulmonary function test results, high-resolution computed tomography findings, histologic findings, occurrence of acute exacerbation of IPF (AE-IPF), and prognosis were evaluated. ResultsThe median patient age was 68 year-old and the median observation period was 44 months. IPF patients with high Ang-2 concentrations showed a significantly lower forced vital capacity (FVC) (2.28 vs. 2.69 L, respectively; p = 0.047) and lower percent diffusion lung capacity for carbon monoxide (%DLCO) (61.4 vs. 81.4%, respectively; p = 0.015) than patients with low Ang-2 concentrations. Serum Ang-2 concentrations were negatively correlated with %DLCO (r = −0.375, p = 0.021) and the change in %FVC in 12 months (r = −0.348, p = 0.043). The Ang-2 concentration was significantly higher in several patients with AE-IPF than in patients in stable condition (p = 0.011). Finally, patients with high Ang-2 concentrations showed a significantly worse prognosis than those with low Ang-2 concentrations (log-rank p = 0.039). Multivariate analysis showed that the serum Ang-2 concentration, but not the Ang-1 concentration, was a significant prognostic factor in patients with IPF (hazard ratio 1.439, p = 0.028). ConclusionIncreases in the serum Ang-2 concentration were associated with disease progression and poor prognosis in patients with IPF.

Serum Angiopoietin-2 and C-reactive protein as biomarkers of acute exacerbations of chronic obstructive pulmonary diseases

ObjectivesTo evaluate the role of serum Angiopoietin-2 and C-reactive protein as blood biomarkers of acute exacerbation of COPD and to assess if they have a relationship with the severity of COPD and the severity grades of exacerbations. BackgroundRecently, Angiopoietin-2 (Ang-2) was identified as a ligand of the endothelial receptor tyrosine kinase, Tie-2. Ang-2 is an Angiopoietin-1 antagonist that plays a role in vascular destabilization and remodeling, which may increase in some diseases. However, serum Ang-2 levels have not been evaluated in patients with COPD.In this study, we examined serum Ang-2 concentrations in patients with COPD exacerbations and in patients with stable COPD. MethodsThis study was conducted on 36 COPD patients in acute exacerbation, 20 patients with stable COPD and 20 healthy subjects (control group), they were selected from the Shibin-Elkoom Chest Hospital from February 2013 to October 2013. All subjects were subjected to detailed clinical history, thorough clinical examination, Modified British Medical Research Council (mMRC) questionnaire and the COPD Assessment Test questionnaire (CAT) to assess symptoms, plain chest-X-ray (postero-anterior and lateral views). Blood sample for the measurement of Angiopoietin-2 and C-reactive protein by ELISA. ResultsSerum concentrations of Ang-2 and CRP were significantly higher in patients with acute exacerbations of COPD than in those with stable COPD or control subjects. Ang-2 was significantly positively correlated with serum CRP levels but negatively correlated with PaO2 in patients with exacerbations. ConclusionSerum levels of Ang-2 and CRP are significantly elevated during acute exacerbations of COPD, as compared with stable COPD.

Circulating angiopoietin‐2, its soluble receptor Tie‐2, and mortality in the general population

To assess the association of circulating concentrations of angiopoietin-2 (Ang-2) and its soluble receptor Tie-2 (sTie-2) with all-cause, cardiovascular, and cancer mortality in a population-based sample. Angiopoietin-2 and sTie-2 were measured in 3220 participants (1665 women; mean age 54.4 years) in the Study of Health in Pomerania (SHIP). Multivariable adjusted hazard ratios (HRs) for mortality were estimated using Cox proportional hazard models. During a median follow-up of 6.2 years, 217 participants died. Ang-2 levels were positively associated with all-cause mortality [HR 1.29; 95% confidence interval (CI) 1.19-1.39 per 1 SD increment; P < 0.001] and cardiovascular mortality (HR 1.32; 95% CI 1.18-1.49; P < 0.001), but not with cancer mortality (HR 1.08; 95% CI 0.89-1.32; P = 0.416). Levels of sTie-2 were not significantly related to all-cause mortality (HR 1.12; 95% CI 0.98-1.27; P = 0.102). Adding Ang-2 to a prediction model for all-cause mortality with standard risk factors slightly improved discrimination (Δ Harrell's C, 0.008; P < 0.001) but not risk reclassification (continuous net reclassification improvement, -0.015; P = 0.571). In our community-based sample, higher serum Ang-2 concentrations were associated with greater risk for all-cause and cardiovascular mortality, suggesting that subtle increases in Ang-2 levels might reflect processes such as vascular remodelling that are associated with higher mortality risk. Adding Ang-2 to a mortality prediction model only modestly improved discrimination.

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.

Роль циркулирующих ангиогенных факторов в поражении почек при сахарном диабете

This original article contains the authors own data on homeostasis of angiogenic growth factors (vascular endothelial growth factor - VEGF, angiopoietin 1 and 2 - Ang-1, Ang-2) in diabetic kidney disease. The aims of study were evaluation of alteration on serum concentration of circulating VEGF, Ang-l and Ang-2, and of their association with markers of renal damage (albuminuria, glomerular filtration rate) and anemia in patients with diabetes mellitus. We studied 78 patients type I diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Among this group 37patients had chronic kidney disease. The serum level of VEGF was elevated in T1DM patients and was associated with degree of proteinuria. The serum concentration of Ang-2 was higher in patients with chronic kidney disease (T1DM and T2DM), renal failure (T1DM), proteinuria and anemia (T2DM). Ang-2 strongly associated with albuminuria (T1DM and T2DM), glomerular filtration rate (T1DM) and hemoglobin (T2DM). Obtained results demonstrate that levels of VEGF and Ang-2 (but not Ang-1) are raised in patients with diabetic kidney disease and associated with markers of renal damage and anemia. These data indicate the presence of the disturbance of angiogenic growth factors (VEGF, Ang-2) homeostasis and activity in diabetic patients with chronic kidney disease.

Early increase of serum angiopoietin-2 are associated with early progression to death in experimental injury

Severe trauma induces systemic inflammatory response syndrome (SIRS) through the release of proinflammatory mediators. Angiopoietin-2 (Ang-2) is over-produced in sepsis and leads to dysfunction of endothelial cells and subsequent multiple organ dysfunction. In order to define the role of Ang-2 in lethal injury, 45 rabbits were studied; eight were administered anesthesia; 11 were sham-operated and 26 were subject to femoral injury. Concentrations of Ang-2, malondialdehyde (MDA), tumor necrosis factor-alpha (TNFα) and endotoxins (LPS) were determined in serum and of Ang-2 in tissues; vital signs and overall survival were recorded. Bacterial growth was quantitatively assessed in liver, spleen and lung of animal that died. Survival of injured animals was shorter than sham operated ones. Serum concentrations of Ang-2 at 4h was greater among animals where death supervened early, i.e. within 48h after injury than among rabbits that died later. That was also the case for systolic, diastolic and mean arterial pressures. Serum MDA and TNFα and tissue bacterial growth did not differ between rabbits that died early and rabbits that died late. Serum LPS remained below the limit of detection. These results suggest that circulating Ang-2 participates in the pathogenesis of SIRS after injury connected with early haemodynamic instability.

Changes and significance of Serum Angiopoietin-1 and Angiopoietin-2 levels in Patients with coronary heart disease

ObjectiveAngiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) are the members of angiopoietin families. The regulation between Ang-1 and Ang-2 plays an important role in accommodating endothelial cell function and inflammation. Several recent...

513 BIOMARKERS ASSOCIATED WITH LONG TERM CARDIOVASCULAR EVENTS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Numerous recent reports demonstrated that changes in serum levels of angiogenesis-related factors were associated with preeclampsia. Here, we determined the serum concentration of angiopoietin-2 (Ang-2), a natural antagonist of angiopoietin-1 (Ang-1) involved in promoting angiogenesis in the presence of angiogenic stimuli such as vascular endothelial growth factor (VEGF), in women with preeclampsia.The levels of serum Ang-2 and Tie-2, a receptor for Ang-1 expressed on endothelial cells, were determined by enzyme-linked immunosorbent assay.The concentrations of serum Ang-2 were significantly elevated in healthy pregnant women (18.9 ng/mL) as compared to nonpregnant women or women in postpartum period. Increase in the levels of serum Ang-2 was significantly suppressed in preeclamptic women (4.5 ng/mL). The serum Ang-2 concentrations inversely correlated with gestational age in healthy pregnant women, but not in preeclamptic women. The serum Ang-2 concentrations positively correlated with placental weight or mean blood pressure (BP) in healthy pregnant women, but not in preeclamptic women. The serum Ang-2 concentrations inversely correlated with proteinuria in preeclamptic women. The serum concentrations of Tie-2 were not significantly different between preeclamptic and nonpreeclamptic women.These results suggest the potential requirement of circulating Ang-2 in proper formation of placental vasculatures during pregnancy. Although we cannot exclude the possibility that suppression in the increase of serum Ang-2 levels during pregnancy in preeclampsia as a consequence rather than a cause, measurement of serum Ang-2 concentration in pregnant women may serve as a useful marker in the diagnosis and potentially in predicting subsequent development of preeclampsia.

Correlation of angiopoietin-2 and angiopoietin-2 receptor expressions in serum and placenta with preeclampsia

To investigate the correlation of the expressions of angiopoietin-2 (Ang-2) and angiopoietin-2 receptor (Tie-2) in serum and placenta with preeclampsia. From May 2009 to April 2010, 62 women with preeclampsia who delivered in Affiliated Hospital of Qingdao University Medical College were recruited in the study, including 30 women with moderate preeclampsia (MPE group) and 32 women with severe preeclampsia (SPE group). Another 30 healthy pregnant women were taken as control group. ELISA was used to measure the serum Ang-2 in these women. Semiquantitative reverse transcription (RT)-PCR was used to investigate the expressions of Ang-2 mRNA and Tie-2 mRNA in placenta. Western blot was used to determine the expression of Ang-2 protein in placenta. (1) The serum concentrations of Ang-2 in MPE group and SPE group were (5.4 ± 1.8) µg/L and (5.1 ± 1.7) µg/L, respectively. Both were significantly lower than that in control group (16.2 ± 4.5) µg/L (P < 0.01). There was no significant difference between MPE group and SPE group (P > 0.05). (2) The expressions of Ang-2 mRNA in placenta of MPE group (2.1 ± 0.7) and SPE group (2.0 ± 0.6) were both significantly lower than that of control group (5.8 ± 0.8; P < 0.01). But there was no significant difference in Ang-2 mRNA expression between MPE group and SPE group (P > 0.05). (3) No significant difference was found in the expressions of Tie-2 mRNA in placenta among MPE group (1.33 ± 0.04), SPE group (1.35 ± 0.05) and control group (1.34 ± 0.04; P > 0.05). (4) The expressions of Ang-2 protein in placenta of MPE group (2.0 ± 0.8) and SPE group (2.0 ± 0.8) were both significantly lower than that of control group (5.7 ± 0.9; P < 0.01), while no significant difference was found between MPE group and SPE group (P > 0.05). (5) In MPE group and SPE group, the serum concentrations of Ang-2 were positively correlated with the levels of Ang-2 mRNA and Ang-2 protein in placenta (r = 0.651, 0.627; P < 0.01). Decreased expressions of Ang-2 mRNA and Ang-2 protein in placenta reduced serum concentration of Ang-2. Low expression of Ang-2 may be involved in the pathophysiological process of preeclampsia by affecting the formation of placenta in early pregnancy.