Endostatin Concentrations Research Articles

Serum Endostatin Levels in Oral Squamous Cell Carcinoma.

Endostatin is a C-terminal proteolytic fragment of collagen XVIII and, as with angiostatin and thrombospondin, is known as an antiangiogenic agent. The aim of this study was to assess the level of serum endostatin in patients with oral squamous cell carcinoma (SCC), and its association with the clinicopathological characteristics of the tumor. Using an enzyme-linked immunosorbent assay (ELISA) kit, we investigated the circulating levels of endostatin in the blood serum of 45 patients with oral SCC and 45 healthy controls. The mean level of serum endostatin in patients was significantly lower (68.8±85 ng/ml) than in healthy controls (175.6±73 ng/ml) (P<0.001). Serum endostatin levels were significantly lower in patients with lymph node metastasis compared with patients without lymph node metastasis (P<0.001). In addition, serum endostatin level was associated with higher histological grade (P<0.001). There were no apparent correlations between serum endostatin concentration and clinicopathological features such as age, gender, and tumor stage (P>0.05). Findings of the present study suggest the prognostic and anti-metastatic role of endostatin, and this may be used as a tool for monitoring tumor progression.

Changes in serum vascular endothelial growth factor and endostatin concentrations associated with circulating endothelial progenitor cells after acute ischemic stroke.

Angiogenesis is an important pathophysiological response to cerebral ischemia, and can be modulated by vascular endothelial growth factor (VEGF) and endostatin. Circulating endothelial progenitor cells (EPCs) also play an important role as an endogenous repair mechanism for ischemic injury. We sought to investigate early changes in the expression of VEGF and endostatin in serum and the circulating EPCs in patients with acute ischemic stroke (AIS) and analyzed the relations between them. The peripheral blood and serum samples were obtained from 30 patients at 1, 3, 5 and 7 d after AIS. Flow cytometry was used to quantify EPCs, and VEGF and endostatin were measured by enzyme linked immunosorbent assay. Correlation analysis was performed to assess the relations between them. Receiver operating characteristic (ROC) curve was used to appraise the value of EPCs levels in predicting the 90-day prognosis after AIS. Compared with control subjects, circulating EPCs numbers increased from a very lower initial level (P < 0.001) until 7 d after AIS. Serum VEGF and endostatin levels increased and peaked at 3 d and 5 d post-stroke (both P < 0.001), respectively. A significant correlation (P = 0.001) was found between peak serum VEGF concentration and peak endostatin concentration. VEGF/endostatin ratio at day 1 and day 3 after AIS significantly correlated with circulating EPCs numbers at day 5 (P < 0.001) and day 7 post-stroke (P < 0.001). ROC curve analysis suggested that circulating EPCs number at day 7 had a significantly predictive power for good prognosis. VEGF and endostatin may mediate EPCs proliferation in the early phase of ischemic stroke, and the circulating EPCs levels can be a predictor of clinical outcome in AIS.

Diagnostic Values of sVEGFR-1 and Endostatin in Malignant Pleural Effusions in Patients with Lung Cancer.

The diagnosis of malignant pleural effusion (MPE) remains a common clinical challenge because of the sensitivity of conventional cytology for the detection is insufficient. Thus, a sensitive clinical marker for diagnosis is required. The aim of this study was to assess the role of two anti-angiogenic cytokines, soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and endostatin, in diagnosing MPE. Effusion samples from 44 patients with MPE caused by lung cancer and from 36 patients with benign pleural effusion (BPE) were collected. The concentrations of sVEGFR-1 and endostatin in pleural fluid were determined by an enzyme-linked immunosorbent assay (ELISA). The diagnostic performance was measured by receiver operating characteristic curves (ROCs). The levels of sVEGFR-1 and endostatin in MPE due to lung cancer were significantly higher than those in BPE (p < 0.05). The sensitivity and specificity of endostatin were 52.27% and 86.11%, respectively, while for sVEGFR-1, the sensitivity was 88.64% and the specificity was 58.33%. Interestingly, the combination of sVEGFR1 and endostatin produced better sensitivity and specificity of 72.73% and 83.33%, respectively. In addition, the levels of sVEGFR-1 and endostatin were significantly related to each other (p < 0.05), and the levels of endostatin in bloody effusions were significantly higher than those in non-bloody effusions (p < 0.05). Our study indicated that the levels of sVEGFR-1 and endostatin were significantly elevated in MPE. The combined detection of sVEGFR-1 and endostatin may be useful in the diagnosis of MPE.

Deciphering the anti-angiogenic effect of endostatin/cyclophosphamide to normalize tumor micrangium through notch signaling pathway in colon cancer.

BackgroundThe invasion of colon cancer is associated with the tumor angiogenesis. Endostatin is an important anti-angiogenic agent, and the additive effect of endostatin with a chemotherapeutic agent, cyclophosphamide, on micrangium has not been established.MethodsMale BALB/c strain nude mice were injected with human colorectal carcinoma cells (HCT-116). The mice were divided into four groups (n = 15, each group) and were treated with different concentrations of endostatin (15, 10, and 5 mg/kg/day), cyclophosphamide (20, 10, and 5 mg/kg/day), and combination of endostatin/cyclophosphamide (15 + 20, 15 + 10, and 15 + 5 mg/kg/day). The tumor inhibition rate was evaluated, followed by the quantification of messenger ribonucleic acid (mRNA) and protein expression of notch signaling components NOTCH-1, NOTCH-3, NOTCH-4, JAG-1, DLL-4, Hes-1, and Hey-1 using quantitative polymerase chain reaction (qPCR). The protein expression of NOTCH-3, JAG-1, and DLL-4 was confirmed using western blotting. Microvessel density (MVD) was evaluated to detect micrangium following the treatment.ResultsThe endostatin/cyclophosphamide-treated samples exhibited an additive effect on the tumor inhibition rate and the microvessel count. NOTCH-1, NOTCH-3, NOTCH-4, JAG-1, Hes-1, and Hey-1 expression levels were highly correlated and downregulated in the treated samples, whereas DLL-4 expression was upregulated that accounted for its anti-angiogenic property.ConclusionsThe combination treatment of colon cancer with endostatin and a chemotherapeutic agent, cyclophosphamide proves to be an efficient therapeutic strategy to inhibit the rapid vasculature formation confirmed by the differential expression of notch signaling components.

Arterial Hypertension Is Characterized by Imbalance of Pro-Angiogenic versus Anti-Angiogenic Factors.

ObjectiveHypertension is the most common cardiovascular disease and the main risk factor for stroke, peripheral arterial disease, arterial aneurysms and kidney disease. It has been reported recently that hypertensive patients and animals are characterized by decreased density of arterioles and capillaries in the tissues, called rarefaction. Rarefaction significantly increases peripheral resistance which results in elevated blood pressure, leads to vessel damage and induction of inflammation. Therefore, we hypothesized that hypertension is associated with decreased serum concentration of physiological pro-angiogenic factors and concomitant increased production of angiogenesis inhibitors.Materials and Methods82 patients diagnosed with hypertension and 34 healthy volunteers were recruited to the study. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) techniques were used to measure serum levels of the following cytokines: endostatin, vascular endothelial growth factor (VEGF), interleukin 8 (IL-8), angiogenin, and basic fibroblast growth factor (bFGF).ResultsHypertensive patients were characterized by increased serum concentration of endostatin which is an anti-angiogenic factor. In addition, hypertension was associated with decreased levels of physiological pro-angiogenic mediators such as: angiogenin and bFGF. The hypertensive group was also characterized by elevated levels of CRP, VEGF and IL-8 that are the hallmarks of inflammation.ConclusionsPresented results show that hypertension is characterized by imbalance of pro-angiogenic and anti-angiogenic factors in the background of inflammation.

Endostatin level in cerebrospinal fluid of patients with Alzheimer's disease.

The aim of this study was to measure the level of endostatin, a fragment of collagen XVIII that accumulates in the brain of patients with Alzheimer's disease (AD), in the cerebrospinal fluids (CSF) of patients with neurodegenerative diseases. The concentrations of total protein, endostatin, amyloid-β1-42 peptide, tau, and hyperphosphorylated tau proteins were measured by enzyme-linked immunosorbent assay in CSF of patients with AD (n = 57), behavioral frontotemporal dementia (bvFTD, n = 22), non AD and non FTD dementia (nAD/nFTD, n = 84), and 45 subjects without neurodegenerative diseases. The statistical significance of the results was assessed by Mann-Whitney and Kruskal and Wallis tests, and by ROC analysis. The concentration of endostatin in CSF was higher than the levels of the three markers of AD both in control subjects and in patients with neurodegenerative diseases. The endostatin/amyloid-β1-42 ratio was significantly increased in patients with AD (257%, p < 0.0001) and nAD/nFTD (140%, p < 0.0001) compared to controls. The endostatin/tau protein ratio was significantly decreased in patients with AD (-49%, p < 0.0001) but was increased in bvFTD patients (89%, p < 0.0001) compared to controls. In the same way, the endostatin/hyperphosphorylated tau protein ratio was decreased in patients with AD (-21%, p = 0.0002) but increased in patients with bvFTD (81%, p = 0.0026), compared to controls. The measurement of endostatin in CSF and the calculation of its ratio relative to well-established AD markers improve the diagnosis of bvFTD patients and the discrimination of patients with AD from those with bvFTD and nAD/nFTD.

Prognostic values of VEGF and endostatin with malignant pleural effusions in patients with lung cancer.

Angiogenesis is important in malignant pleural effusion (MPE) formation and it is regulated by a number of pro- and anti-angiogenic cytokines. The purpose of this study was to evaluate the prognostic value of angiogenic factor vascular endothelial growth factor (VEGF) and angiogenesis inhibitor endostatin in lung cancer patients with MPE, and investigate the relationship between these two kinds of agent. Using enzyme-linked immunoadsorbent assay, the concentrations of VEGF and endostatin were measured in pleural effusions (PE) and serum from a total of 70 lung cancer patients with MPE and 20 patients with tuberculosis. Compared to patients with tuberculosis, the levels of VEGF and endostatin in both PE and serum were significantly higher in patients with lung cancer. There were statistically significant correlations between VEGF levels in PE and serum (r=0.696, <0.001), endostatin levels in PE and serum (r=0.310, p=0.022), and VEGF and endostatin levels in PE (r=0.287, p=0.019). Cox multivariate analysis revealed that elevated pleural VEGF and endostatin levels and serum endostatin level were independent predictors of shorter overall survival. Both pro- and anti-angiogenic factors are likely contributors to PE formation. Our results suggest that the levels of VEGF and endostatin in PE, together with endostatin in serum, may be potential prognostic parameters for lung cancer patients with MPE.

Serum Factors of Angiogenesis and the Growth of Fibroblasts in Osteogenic Sarcoma

ABSTRACT Aim: The purpose of our research was to study the levels of endostatin, FFG 1, VEGF in osteogenic sarcoma patients' peripheric blood serum before conducting treatment in order to detect their possible relationship with clinical characteristic diseases and prognosis. Methods: We have studied 76 patients with osteogenic sarcoma of tubular bones. The received data showed that the levels in blood serum of patients with osteogenic sarcoma FFG-1 and endostatin composed 96±14.5pg/ml and 146.7±3.8 ng/ml, respectively, which compared with 287.8±1.9 pk/ml and 56.5±0.98 ng/ml in healthy people. Results: The expression of FFG-1 is possible and endostatin may have a connection with pathogenetic changes dealing with the growth of bone tumors. Serum concentrations of VEGF in 71.5% patients with osteogenic sarcoma were increased by 14.3 times (520±68.5 ng/ml in patients) compared with the data from the control group (36.3±0.5 ng/ml). On the basis of laboratory and clinical research the threshold concentration and connection of serum VEGF, FFG-1 and endostatin with clinical course and prognosis of disease were determined. At the level of FFG-1 less than 35.0 pg/ml 3-year survival was 94% but more than 350 pg/ml - 64%. There is also a relationship between the level of malignization of tumor and contents of VEGF in blood serum;, dependence between the concentration of VEGF, metastatic potential of osteogenic sarcoma and the term of metastasis were detected. Conclusions: Comparative research of VEGF, FFG-1 and endostatin levels in primary tumor of patients with OS can be used as criteria of prognosis of disease and introduced into the scheme of complex therapy preparations, so influencing the expression of VEGF, FFG-1 and endostatin in patients with primary neoplasms of bones with the purpose of increasing the efficacy of therapy. Disclosure: All authors have declared no conflicts of interest.

Serum endostatin levels are elevated in colorectal cancer and correlate with invasion and systemic inflammatory markers.

Background:Endostatin, a fragment of collagen XVIII, is an endogenous angiogenesis inhibitor with anti-tumour functions. However, elevated circulating endostatin concentrations have been found in several human cancers including colorectal cancer (CRC).Methods:Serum endostatin levels were measured by enzyme-linked immunoassay from a series of 143 patients with CRC and from 84 controls, and correlated with detailed clinicopathological features of CRC, serum leukocyte differential count and C-reactive protein (CRP) levels.Results:Patients with CRC had higher serum endostatin levels than the controls (P=0.005), and high levels associated with age, tumour invasion through the muscularis propria and poor differentiation, but not with metastases. Endostatin levels showed a positive correlation with the markers of systemic inflammatory response and a negative correlation with the densities of tumour-infiltrating mast cells and dendritic cells. Collagen XVIII was expressed in tumour stroma most strikingly in blood vessels and capillaries, and in the muscle layer of the bowel wall.Conclusions:Elevated endostatin levels in CRC correlate with systemic inflammation and invasion through the muscularis propria. Increased endostatin level may be a result of invasion-related cleavage of collagen XVIII expressed in the bowel wall. The negative correlations between serum endostatin and intratumoural mast cells and immature dendritic cells may reflect angiogenesis inhibition by endostatin.

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Cardiovascular diseases have been associated with depression in later life, and a potential mechanism is inhibition of angiogenesis. We designed this study to determine if depression is associated with higher serum concentration of endostatin, an endogenous angiogenesis inhibitor. We performed a cross-sectional examination of a random sample of men aged 69-86 years. Those who scored 7 or higher on the 15-item Geriatric Depression Scale were deemed depressed. We determined the concentration of serum endostatin using a reproducible assay. Other measures included age, education, body mass index, smoking, history of depression, use of antidepressants, hypertension, diabetes, coronary heart disease and stroke, high sensitivity C-reactive protein, plasma homocysteine, triglycerides and cholesterol. We used logistic regression to investigate the association between endostatin and depression, and adjusted the analyses for confounding factors. Our sample included 1109 men. Sixty-three (5.7%) men were depressed. Their serum endostatin was higher than that of nondepressed participants (p = 0.021). Men in the highest decile of endostatin had greater adjusted odds of depression (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.03-3.06). A doubling of endostatin doubled the odds of depression (OR 1.93, 95% CI 1.31-2.84). The probability of depression increased with the concentration of endostatin in a log-linear fashion up to a maximum of about 20%-25%. The cross-sectional design limits the study's ability to ascribe causality to the association between high endostatin and depression. Serum endostatin is associated with depression in older men. It remains to be established whether correction of this imbalance is feasible and could decrease the prevalence of depression in later life.

Endostatin and cathepsin-V in bronchoalveolar lavage fluid of patients with pulmonary sarcoidosis.

Recently, it has been reported that lack of cathepsins prevent the development of lung granulomas in a mouse model of Besnier-Boeck-Schaumann (BBS) disease, sarcoidosis. There is no data about cathepsin V (Cath V) in bronchoalveolar lavage fluid (BALF) in humans. Endostatin is a novel inhibitor of lung epithelial cells. The role of this protein in BBS is not determined. The aim of this study was to evaluate the concentration of endostatin, Cath V, and IL-18 in BALF of BBS patients. We studied 22 BBS patients (Stage 2). The control group consisted of 20 healthy subjects. Cath V concentration was lower in BBS than in healthy group (16.03±8.60 vs. 32.25±21.90 pg/ml, p=0.004). Both endostatin and IL-18 levels were higher in BBS than in the control group (0.88±0.30 vs. 0.29±0.04 ng/ml, p=0.028; 40.37±31.60 vs. 14.61±1.30 pg/ml, p=0.007, respectively). In BBS there were correlations between the levels of endostatin and IL-18 (r=0.74, p=0.001) as well as endostatin and DLCO (diffusing capacity for carbon monoxide) (r=-0.6, p=0.013). Receiver-operating characteristic (ROC) curves were applied to find the cut-off for the BALF levels of Cath V, endostatin, and IL-18. We conclude that Cath V and endostatin may represent an index of pulmonary sarcoidosis activity.

Serum Endostatin Concentrations Are Higher in Men with Symptoms of Intermittent Claudication

Objectives. A cleavage fragment of collagen XVIII, endostatin, is released into the circulation and has been demonstrated to have antiangiogenic effects in animal models. We hypothesized that circulating endostatin would be increased in patients with symptoms of lower limb peripheral artery disease. Design. Cross-sectional study. Participants. Community dwelling older men. Measurements. Intermittent claudication was defined using the Edinburgh Claudication Questionnaire (ECQ). Serum endostatin was measured by a commercial ELISA. The association of serum endostatin with intermittent claudication was examined using logistic regression adjusting for age, diabetes, hypertension, dyslipidemia, coronary heart disease, and stroke. Results. Serum endostatin was measured in 1114 men who completed the ECQ. 106 men had intermittent claudication, 291 had atypical pain, and 717 had no lower limb pain. Mean (±standard deviation) serum endostatin concentrations (ng/mL) were 145.22 ± 106.93 for men with intermittent claudication, 129.11 ± 79.80 for men with atypical pain, and 116.34 ± 66.57 for men with no lower limb pain; P < 0.001. A 70 ng/mL increase in endostatin was associated with a 1.17-fold rise in the adjusted odds of having intermittent claudication (OR 1.17, 95% confidence interval 1.00–1.37, and P = 0.050). Conclusions. Serum endostatin is raised in older men who have symptoms of intermittent claudication. The role of endostatin in the genesis and outcome of peripheral artery disease requires further investigation.

Association of endostatin with mortality in patients with chronic heart failure

Experimental data imply that in decompensated heart failure (HF), the anti-angiogenic factor endostatin is increased. This study aimed to investigate whether the angiogenesis inhibitor endostatin is related to the risk of all-cause mortality in a prospective cohort study of chronic HF patients. In this prospective observational cohort study, endostatin serum concentrations were determined in patients with chronic HF. Mortality data were recorded during a median follow-up of 31months. One fifty one patients were included. The overall mortality rate was 20%. Baseline endostatin concentrations >245ng/mL were associated with higher risk of all-cause mortality [HR 8·7 (95% CI 2·5-30·0); P=0·001] in the multivariate analysis as compared to endostatin concentrations ≤245ng/mL. When both endostatin and NT-proBNP were above the calculated cut-off of 245ng/mL and 2386pg/mL, respectively, the prognostic utility of both biomarkers increased [HR 40·8 (95% CI 4·7-354·6); P=0·001] compared with values lower than the cut-offs. Serum endostatin concentrations are independently associated with all-cause mortality. Furthermore, combination of endostatin and NT-proBNP discriminates patients at high risk.

Circulating angiogenic biomolecules at rest and in response to upper-limb exercise in individuals with spinal cord injury

ObjectiveIndividuals with spinal cord injury (SCI) show structural and functional vascular maladaptations and muscle loss in their lower limbs. Angiogenic biomolecules play important roles in physiological and pathological angiogenesis, and are implicated in the maintenance of muscle mass. This study examined the responses of angiogenic molecules during upper-limb aerobic exercise in patients with SCI and in able-bodied (AB) individuals.MethodsEight SCI patients with thoracic lesions (T6–T12, ASIA A) and eight AB individuals performed an arm-cranking exercise for 30 minutes at 60% of their VO2max. Plasma concentrations of vascular endothelial growth factor (VEGF-A165), VEGF receptor 1 (sVEGFr-1), VEGF receptor 2 (sVEGFr-2), metalloproteinase 2 (MMP-2), and endostatin were measured at rest, after exercise, and at 1.5 and 3.0 hours during recovery.ResultsThe two-way analysis of variance showed non-significant main effects of “group” and significant main effects of “time/exercise” for all angiogenic biomolecules examined (P < 0.01–0.001). The arm-cranking exercise significantly increased plasma concentrations of VEGF, sVEGFr-1, sVEGFr-2, MMP-2, and endostatin in both groups (P < 0.001–0.01). The magnitude of the increase was similar in both patients with SCI and AB individuals, as shown by the non-significant group × time interaction for all angiogenic parameters.ConclusionsUpper-limb exercise (arm-cranking for 30 minutes at 60% of VO2max) is a sufficient stimulus to trigger a coordinated circulating angiogenic response in patients with SCI. The response of angiogenic molecules to upper-limb aerobic exercise in SCI appears relatively similar to that observed in AB individuals.

Whole-Body Vibrations Do Not Elevate the Angiogenic Stimulus when Applied during Resistance Exercise

Knowledge about biological factors involved in exercise-induced angiogenesis is to date still scanty. The present study aimed to investigate the angiogenic stimulus of resistance exercise with and without superimposed whole-body vibrations. Responses to the exercise regimen before and after a 6-week training intervention were investigated in twenty-six healthy male subjects. Serum was collected at the initial and final exercise sessions and circulating levels of matrix metalloproteinases (MMP) -2 and -9, Vascular Endothelial Growth Factor (VEGF) and endostatin were determined via ELISA. Furthermore, we studied the proliferative effect of serum-treated human umbilical vein endothelial cells in vitro via BrdU-incorporation assay. It was found that circulating MMP-2, MMP-9, VEGF and endostatin levels were significantly elevated (P<0.001) from resting levels after both exercise interventions, with higher post-exercise VEGF concentrations in the resistance exercise (RE) group compared to the resistive vibration exercise (RVE) group. Moreover, RE provoked increased endothelial cell proliferation in vitro and higher post-exercise circulating endostatin concentrations after 6 weeks of training. These effects were elusive in the RVE group. The present findings suggest that resistance exercise leads to a transient rise in circulating angiogenic factors and superimposing vibrations to this exercise type might not further trigger a potential signaling of angiogenic stimulation in skeletal muscle.

Endostatina sérica en preeclampsia y eclampsia

ObjectiveTo compare serum endostatin concentrations in eclamptic, pre-eclamptic and normotensive pregnant women. Materials and methodThe study included 30 patients with mild preeclampsia (group A), 30 patients with severe pre-eclampsia (group B), and 30 patients with eclampsia (group C). A control group, consisting of 30 healthy pregnant women of similar age and body mass index to the studiy groups, was selected (group D). Only nuliparous patients were included. Blood samples were collected for serum endostatin determination from all patients before delivery, and from the study groups immediately after diagnosis. ResultsHigher values of endostatin were observed in eclamptic patients together with severe pre-eclamptic patients. Lower values were found in mild pre-eclamptic patients. The study groups had significantly higher values of endostatin compared with the control group (P<.05). Linear regression analysis, found that factors that significantly affected plasma endostatin concentrations were uric acid and 24-hour proteinuria. ConclusionThe findings of this study showed that eclamptic and pre-eclamptic patients had higher serum endostatin concentrations than normotensive pregnant women.

Endostatin/Collagen XVIII Is Increased in Cerebrospinal Fluid after Severe Traumatic Brain Injury

Recent studies have suggested that endogenous angiogenesis inhibitor endostatin/collagen XVIII might play an important role in the secondary brain injury following traumatic brain injury (TBI). In this study, we measured endostatin/collagen XVIII concentrations serially for 1 week after hospitalization by using the enzyme-linked immunosorbent assay method in the cerebrospinal fluid (CSF) of 30 patients with TBI and a Glasgow Coma Scale (GCS) score of 8 or less on admission. There was a significant trend toward increased CSF levels of endostatin after TBI versus control from 72 h after injury. In patients with GCS score of 3–5, CSF endostatin concentration was substantially higher at 72 h after injury than that in patients with GCS score of 6–8 (P < 0.05) and peaked rapidly at day 5 after injury, but decreased thereafter. The CSF endostatin concentration in 12 patients with an unfavorable outcome was significantly higher than that in 18 patients with a favorable outcome at day 5 (P = 0.043) and day 7 (P = 0.005) after trauma. Receiver operating characteristic curve analysis suggested a reliable operating point for the 7-day CSF endostatin concentration predicting poor prognosis to be 67.29 pg/mL. Our preliminary findings provide new evidence that endostatin/collagen XVIII concentration in the CSF increases substantially in patients with sTBI. Its dynamic change may have some clinical significance on the judgment of brain injury severity and the assessment of prognosis. This trial is registered with the ClinicalTrials.gov Identifier: NCT01846546.

Vascular Endothelial Growth Factor and Endostatin in Synovial Fluid of Various Arthritic Conditions

Introduction: Rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoarthritis (OA), and gout are common forms of arthritic conditions. Angiogenesis via involvement of many regulatory cytokines and angiogenesis inhibitors is important in the pathogenesis of arthritis. The goal of this study is to compare two major angiogenetic factors, vascular endothelial growth factor (VEGF) and endostatin, in synovial fluid (SF) among various arthritic conditions. Patients and Methods: We collected SF through arthrocentesis of knees in patients with RA, AS, OA and gout. The concentrations of VEGF and endostatin in synovial fluid were analyzed using enzyme-linked immunosorbent assay. The influence of disease activity at the time of arthrocentesis was assessed by comparing peripheral blood white blood cell count (WBC), synovial WBC (SWBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) with levels of VEGF and endostatin. Results: Synovial VEGF was the highest in RA, followed by gout, AS, and OA; however, endostatin was the highest in gout, then AS, RA, and OA. VEGF had positive correlation with SWBC and endostatin had negative correlation with SWBC. However, there was no correlation between either synovial VEGF or endostatin and ESR or CRP level. Conclusion: The concentrations of VEGF and endostatin in synovial fluid varied among different inflammatory forms of arthritis, and were related with inflammation status.

Antiangiogenic Shift in Vitreous after Vitrectomy in Patients with Proliferative Diabetic Retinopathy

We determined whether the concentrations of VEGF, erythropoietin, and endostatin in the vitreous are altered after vitrectomy in patient with proliferative diabetic retinopathy (PDR). We measured the levels of VEGF, erythropoietin, and endostatin by sandwich ELISA in vitreous samples collected from 38 eyes of 33 patients with PDR before pars plana vitrectomy (without IOL implantation) and the same 38 eyes during IOL implantation 3.1 to 25.7 (mean 6.7) months after the initial vitrectomy. The mean vitreous levels of VEGF (964.5 pg/mL) and erythropoietin (1359.5 pg/mL) in the samples collected before vitrectomy were significantly higher in patients with PDR than in the control patients (0.68 and 70.7 pg/mL, respectively; P < 0.01). The levels of VEGF (292.5 pg/mL) and erythropoietin (557.9 pg/mL) in the samples from eyes with PDR collected at the time of IOL implantation were significantly lower than those collected before vitrectomy (P < 0.01). In contrast, the changes in the level of endostatin were not significant after vitrectomy. The VEGF and erythropoietin levels in the vitreous fluid from patients with PDR were correlated inversely with the interval between the initial vitrectomy and the time of the IOL implantation. The significant decrease in the intravitreal concentration of VEGF and erythropoietin, and an absence of a significant change in the endostatin indicated a shift in the antiangiogenic balance in the vitreous of patients with PDR after successful vitrectomy.

Elevated Peripheral Blood Plasma Concentrations of Tie-2 and Angiopoietin 2 in Patients with Neuroendocrine Tumors

BackgroundGastro-entero-pancreatic/neuroendocrine (NET) tumors are highly vascularized neoplasms. However, our knowledge concerning circulating levels of the angiogenic factors in NET patients still remains insufficient.MethodsThe aim of this study was to measure plasma concentrations of VEGF, angiopoietin 1 (Ang-1), angiopoietin 2 (Ang-2), soluble Tie-2, endostatin, osteopontin (OPN) and chromogranin A (CgA) in 36 NET patients and 16 controls.ResultsOnly the plasma concentrations of Tie-2 and CgA were higher in NET patients as compared to controls. These levels were within the reference range in controls; however one control demonstrated slightly elevated Tie-2 and 4 elevated CgA. Similarly, in the subgroup of patients with carcinoid syndrome, only Tie-2 and CgA concentrations were higher than those in patients with non-functioning NETs. In turn, in the subgroup of metastatic patients, only Ang-2 levels were higher than in those with localized disease. A positive correlation was found between Ang-2 and Tie-2 levels in metastatic patients and between Ang-1 and Tie-2 in localized NETs.ConclusionsThe plasma concentration of Tie-2 is proposed as an additional marker for NET patients and seems to be similarly effective as the currently used CgA level. Moreover, higher plasma levels of Ang-2 together with the positive correlation between Ang-2 and Tie-2 levels in metastatic subjects, implies that cases with a Tie-2 level above the upper limits, together with higher level of Ang-2 seem to be highly predictive of metastases.