Endostatin Levels Research Articles

Serum Vascular Endothelial Growth Factor and Endostatin as an Adjunct to Clinical Decision Making in Managing Radiation-induced Changes Post Gamma Knife Radiosurgery in Spetzler Martin Grade 3 Arteriovenous Malformations Patients: A Pilot Study

BackgroundRadiation induced changes (RIC) are the most common complications observed post GKRS and may be observed within 6-18months post procedure. It has been observed that almost one third of RICs are symptomatic and half of them are persistent. There is no way to predict which patients will develop these changes and to what extent.This was a prospective analytical pilot study with the aim of understanding the role of Serum Vascular Endothelial Growth Factor and Endostatin as a predictive factor for clinically symptomatic RIC in intracranial AVMs Spetzler Martin (SM) grade 3 being managed with primary Gamma Knife radiosurgery.Total of 15 patients were analysed. 60% of them had a history of bleed. The median volume of AVM Nidus was 4.36 cc. One third of the patients had no imaging changes suggestive of RIC at 1 year follow up and 2 of the patients had symptomatic RIC needing intervention. Before Gamma Knife, the median values of serum concentration of Endostatin and VEGF are 34.98 ng/mL and 168.37 pg/mL respectively . The serum values of VEGF at 1 month post GKRS was much less than the pre GKRS values but not found to be predictive of RIC. No correlation could be observed with the levels of serum endostatin and RIC.Some patients may develop resistant oedema and necrosis post GKRS for intracranial AVMs which may warrant medical and surgical intervention. Serum biomarkers like VEGF and Endostatin may vary in post GKRS period fpo can be used to identify at risk cases, however more studies are needed to decide on appropriate time of sampling and identify clinically relevant predictive factors.

Tofacitinib Regulates Endostatin via Effects on CD147 and Cathepsin S.

Angiogenesis is critical for rheumatoid arthritis (RA) progression. The effects of tofacitinib, a JAK-STAT inhibitor used for RA treatment, on angiogenesis in RA are unclear. We, therefore, evaluated the levels of angiogenic factors in two systems of a human co-culture of fibroblast (HT1080) and monocytic (U937) cell lines treated with tofacitinib and in serum samples from RA patients before and after six months of tofacitinib treatment. Tofacitinib reduced CD147 levels, matrix metalloproteinase-9 (MMP-9) activity, and angiogenic potential but increased endostatin levels and secreted proteasome 20S activity. In vitro, tofacitinib did not change CD147 mRNA but increased miR-146a-5p expression and reduced STAT3 phosphorylation. We recently showed that CD147 regulates the ability of MMP-9 and secreted proteasome 20S to cleave collagen XVIIIA into endostatin. We show here that tofacitinib-enhanced endostatin levels are mediated by CD147, as CD147-siRNA or an anti-CD147 antibody blocked proteasome 20S activity. The correlation between CD147 and different disease severity scores supported this role. Lastly, tofacitinib reduced endostatin' s degradation by inhibiting cathepsin S activity and recombinant cathepsin S reversed this in both systems. Thus, tofacitinib inhibits angiogenesis by reducing pro-angiogenic factors and enhancing the anti-angiogenic factor endostatin in a dual effect mediated partly through CD147 and partly through cathepsin S.

Collagen 18A1/Endostatin Expression in the Progression of Right Ventricular Remodeling and Dysfunction in Pulmonary Arterial Hypertension.

Numerous studies have demonstrated that endostatin (ES), a potent angiostatic peptide derived from collagen type XVIII α 1 chain and encoded by COL18A1, is elevated in pulmonary arterial hypertension (PAH). It is important to note that elevated ES has consistently been associated with altered hemodynamics, poor functional status, and adverse outcomes in adult and pediatric PAH. This study used serum samples from patients with Group I PAH and plasma and tissue samples derived from the Sugen/hypoxia rat pulmonary hypertension model to define associations between COL18A1/ES and disease development, including hemodynamics, right ventricle (RV) remodeling, and RV dysfunction. Using cardiac magnetic resonance imaging and advanced hemodynamic assessments with pressure-volume loops in patients with PAH to assess RV-pulmonary arterial coupling, we observed a strong relationship between circulating ES levels and metrics of RV structure and function. Specifically, RV mass and the ventricular mass index were positively associated with ES, whereas RV ejection fraction and RV-pulmonary arterial coupling were inversely associated with ES levels. Our animal data demonstrate that the development of pulmonary hypertension is associated with increased COL18A1/ES in the heart as well as the lungs. Disease-associated increases in COL18A1 mRNA and protein were most pronounced in the RV compared with the left ventricle and lung. COL18A1 expression in the RV was strongly associated with disease-associated changes in RV mass, fibrosis, and myocardial capillary density. These findings indicate that COL18A1/ES increases early in disease development in the RV and implicates COL18A1/ES in pathologic RV dysfunction in PAH.

Angiogenic Regulators during Alpine Skiing Training

Purpose: The present study evaluates angiogenesis response through the determination of acute changes in hypoxia inducible factor 1 alpha, vascular endothelial growth factor, erythropoietin and endostatin levels measured after both slalom and giant slalom trainings. Material and Methods: A total of 20 volunteer male athletes over the age of 18 years with no health problems, and with international alpine skiing competition experience were included in the study. At the outset, the height, body weight and VO2max values of the volunteers was measured, and a giant slalom training lasting 2.5 hours was performed after a week on a giant slalom course. The volunteers were then asked not to exercise for a week, and slalom training was performed lasting 2.5 hours on a slalom course. The endostatin, erythropoietin, hypoxia inducible factor 1 alpha, and vascular endothelial growth factor levels of the volunteers were examined from 5 ml venous blood samples drawn into biochemistry tubes 20 minutes before and as soon as trainings over both the giant slalom and slalom trainings. Results: A significant increase was determined in the hypoxia inducible factor 1 alpha, vascular endothelial growth factor, erythropoietin and endostatin levels after both the giant slalom and slalom trainings (p < 0.05). Conclusion: These increases observed in the angiogenesis markers suggests that a single unit giant slalom and slalom trainings induces angiogenesis responses.

Photobiomodulation Inhibits Ischemia-Induced Brain Endothelial Senescence via Endothelial Nitric Oxide Synthase.

Recent research suggests that photobiomodulation therapy (PBMT) positively impacts the vascular function associated with various cerebrovascular diseases. Nevertheless, the specific mechanisms by which PBMT improves vascular function remain ambiguous. Since endothelial nitric oxide synthase (eNOS) is crucial in regulating vascular function following cerebral ischemia, we investigated whether eNOS is a key element controlling cerebrovascular function and the senescence of vascular endothelial cells following PBMT treatment. Both rat photothrombotic (PT) stroke and in vitro oxygen-glucose deprivation (OGD)-induced vascular endothelial injury models were utilized. We demonstrated that treatment with PBMT (808 nm, 350 mW/cm2, 2 min/day) for 7 days significantly reduced PT-stroke-induced vascular permeability. Additionally, PBMT inhibited the levels of endothelial senescence markers (senescence green and p21) and antiangiogenic factor (endostatin), while increasing the phospho-eNOS (Ser1177) in the peri-infarct region following PT stroke. In vitro study further indicated that OGD increased p21, endostatin, and DNA damage (γH2AX) levels in the brain endothelial cell line, but they were reversed by PBMT. Intriguingly, the beneficial effects of PBMT were attenuated by a NOS inhibitor. In summary, these findings provide novel insights into the role of eNOS in PBMT-mediated protection against cerebrovascular senescence and endothelial dysfunction following ischemia. The use of PBMT as a therapeutic is a promising strategy to improve endothelial function in cerebrovascular disease.

Effects of N-Acetylcysteine on Humanin and Endostatin in Rats Exposed to Formaldehyde.

People are constantly exposed to formaldehyde, a volatile and poisonous gas, in indoor environments. In particular, anatomists, pathologists, histologists, and those involved in embalming are exposed to higher amounts of formaldehyde continuously due to their work. This study aimed to investigate the effect of N-acetylcysteine on endostatin and humanin values in male rats exposed to experimental formaldehyde. In the study, 28 male Spraque-Dawley rats aged 12-14 weeks (seven animals in each group: control group, formaldehyde group, N-acetylcysteine group, formaldehyde+N-acetylcysteine group) were used. Four weeks later, the animals were sacrificed by decapitation. Following decapitation, endostatin and humanin levels in the serum of rats were studied by the enzyme-linked immunoassay (ELISA) method. In all analyses, p<0.05 was accepted as statistically significant. Humanin and endostatin values were checked in the serum of rats. When humanin levels were compared between groups, a statistically significant difference was found between the formaldehyde group and both the control group (p<0.05) and the N-acetylcysteine group (p<0.05). In the formaldehyde+N-acetylcysteine group, it was determined that the humanin level was impaired due to formaldehyde exposure, approaching the control group values with the administered N-acetylcysteine. When the endostatin level was compared between the groups, a statistical significance (p<0.05) was found only between the formaldehyde group and the N-acetylcysteine group. In the formaldehyde+N-acetylcysteine group, it was determined that the endostatin level was impaired due to formaldehyde exposure, approaching the control group values with the administered N-acetylcysteine. In this study, the effects of N-acetylcysteine on humanin and endostatin on rats exposed to formaldehyde were demonstrated for the first time. Formaldehyde exposure negatively affected humanin and endostatin levels in rat sera. N-acetylcysteine ameliorated the negative effects of formaldehyde, bringing humanin and endostatin levels closer to the healthy control group.

Orthostatic hypotension is associated with higher levels of circulating endostatin.

The pathophysiology of orthostatic hypotension (OH), a common clinical condition, associated with adverse outcomes, is incompletely understood. We examined the relationship between OH and circulating endostatin, an endogenous angiogenesis inhibitor with antitumour effects proposed to be involved in blood pressure (BP) regulation. We compared endostatin levels in 146 patients with OH and 150 controls. A commercial chemiluminescence sandwich immunoassay was used to measure circulating levels of endostatin. Linear and multivariate logistic regressions were conducted to test the association between endostatin and OH. Endostatin levels were significantly higher in OH patients (59 024 ± 2513 pg/mL) vs. controls (44 090 ± 1978pg/mL, P < 0.001). A positive linear correlation existed between endostatin and the magnitude of systolic BP decline upon standing (P < 0.001). Using multivariate analysis, endostatin was associated with OH (adjusted odds ratio per 10% increase of endostatin in the whole study population = 1.264, 95% confidence interval 1.141-1.402), regardless of age, sex, prevalent cancer, and cardiovascular disease, as well as traditional cardiovascular risk factors. Circulating endostatin is elevated in patients with OH and may serve as a potential clinical marker of increased cardiovascular risk in patients with OH. Our findings call for external validation. Further research is warranted to clarify the underlying pathophysiological mechanisms.

Circulatory endostatin level and risk of cardiovascular events in patients with end-stage renal disease on hemodialysis.

Endostatin is released during extracellular matrix remodeling and is involved in the development of vascular pathology and cardiovascular (CV) disease. However, the role of circulating endostatin as a biomarker of vascular calcification and CV events in patients undergoing hemodialysis (HD) remains unclear. A total of 372 patients undergoing HD were prospectively recruited. Plasma endostatin levels were measured at baseline, and their associations with circulating mineral bone disease (MBD) biomarkers and abdominal aortic vascular calcification scores were analyzed. The primary endpoint was defined as a composite of CV and cardiac events. Plasma levels of patients in endostatin tertile 3 were significantly associated with low-density lipoprotein cholesterol levels and predialysis systolic blood pressure in multivariate analysis. However, endostatin levels did not correlate with circulating MBD biomarkers or vascular calcification scores. Patients in endostatin tertile 3 had a significantly higher cumulative event rate for the composite of CV events (p = 0.006). Endostatin tertile 3 was also associated with an increased cumulative rate of cardiac events (p = 0.04). In multivariate Cox regression analyses, endostatin tertile 3 was associated with a 4.37-fold risk for composite CV events and a 3.88-fold risk for cardiac events after adjusting for multiple variables. Higher circulating endostatin levels were independently associated with atherosclerotic risk factors but did not correlate with MBD markers or vascular calcification. Higher circulating endostatin levels were associated with a greater risk of composite CV events in patients undergoing HD, and endostatin is a biomarker that helps to determine the high risk of CV events.

Investigation of Vascular Endothelial Growth Factor and Endostatin Levels in Some Rat Tissues in Response to Cold Stress and Diet

Objective: Obesity, the disease of our age, is a condition that occurs when there is an excess of fat tissue in the body. It is not merely a concern about weight gain, but rather a medical issue that elevates the risk of various diseases including heart disease, diabetes, high blood pressure, and certain cancers. This study aimed to explore the impact of a high-fat diet under normal conditions and cold stress, as well as the influence of propolis as a dietary supplement, on vascular endothelial growth factor (VEGF) and endostatin levels in rats fed with propolis. Material and Methods: Thirty-six 3-month-old female Wistar rats (6 rats in each group) sourced from Inonu University Experimental Animal Production and Research Center were utilized for the study. Propolis was administered by gavage, dissolved in water, at a dosage of 2 mL per day for two weeks. Results: The group exhibiting at least a 20% increase in weight due to high-fat diet consumption was categorized as the obese group. Tissues including heart, liver, lung, brown adipose, and white adipose tissues were procured from the obese, propolis-treated, and control groups. Endostatin and vascular endothelial growth factor levels were assessed in the tissues using the ELISA method. The study revealed an elevation in VEGF levels in brown adipose tissue in both cold stress and propolis treatment groups, accompanied by a reduction in white adipose tissue compared to the control group. Additionally, VEGF levels displayed a general increase in lung, liver, and heart tissues. Conversely, endostatin levels, an antiangiogenic factor, decreased in brown adipose tissue while increasing in white adipose tissue. In liver, lung, and heart tissues, endostatin levels exhibited a general decrease. Conclusion: The findings suggest that both cold stress and propolis treatment influence VEGF and endostatin levels in various rat tissues, indicating potential implications for obesity-related conditions and angiogenesis regulation.

Endostatin, soluble tumour necrosis factor receptor 1 and soluble tumour necrosis factor receptor 2 cannot predict new onset of microalbuminuria in patients with type 2 diabetes.

Inflammation and angiogenesis play an important role in the development of early diabetic kidney disease. We investigated the association of soluble Tumour Necrosis Factor Receptor 1 (sTNF-R1), sTNF-R2 and endostatin with new onset microalbuminuria in normoalbuminuric patients with diabetes mellitus type 2. We conducted a case control study to assess serum levels of sTNF-R1, sTNF-R2 and endostatin in 169 patients with new onset microalbuminuria and in 188 matched normoalbuminuric, diabetic controls. Baseline serum samples from participants of the ROADMAP (Randomized Olmesartan and Diabetes Microalbuminuria Prevention) and observational follow-up (ROADMAP-OFU) studies were used. Endostatin and sTNF-R1 but not sTNF-R2 were increased at baseline in patients with future microalbuminuria. In the multivariate analysis, each log2 increment in endostatin levels was associated with an increase of only 6% in the risk of development of microalbuminuria (adjusted HR (95% CI) 1.006 (1.001-1011). sTNF-R1 and sTNF-R2 levels were conversely associated with microalbuminuria, but the results did not reach statistical significance. The respective adjusted HRs (95% CI) were 1.305 (0.928-1.774) and 0.874 (0.711-1.074). sTNF-R1 and sTNF-R2 failed to predict the occurrence of microalbuminuria in normoalbuminuric patients with type 2 diabetes. Likewise, the utility of endostatin in predicting new onset proteinuria is limited.

Increased levels of circulating endostatin are linked to orthostatic hypotension

Abstract Background Orthostatic hypotension (OH) occurs when blood pressure regulation fails. The underlying molecular mechanism of OH remain largely unexplored. Endostatin is a biologically active molecule cleaved by matrix metalloproteinases, elastases and cathepsins from collagen XVIII in the extracellular matrix and inhibits angiogenesis. Circulating levels of endostatin have been proposed to be involved in blood pressure (BP) regulation, by inducing nitric oxide release. To date, the relationship between endostatin and OH have not been examined. Purpose We aimed to investigate circulating levels of endostatin in patients with verified OH by tilt test at a tertiary syncope unit compared with healthy age- and sex-matched controls from the same geographical region. Methods We performed an age- and sex-matched case-control study in 150 patients with OH verified by positive head-up tilt-testing and other cardiovascular autonomic tests at a tertiary syncope unit, and 150 healthy controls with negative active standing tests and no history of syncope, orthostatic intolerance, and endocrine disease. High-sensitivity chemiluminescence sandwich immunoassay was used to measure circulating levels of endostatin in a blinded fashion. Receiver operating characteristic curves were constructed to analyze the discriminative ability of endostatin in OH compared with healthy controls. Multivariate logistic regression was used to assess the association between endostatin, OH and hemodynamic variables adjusting for age and sex. Results Study characteristics are displayed in the Table. Patients with OH had significantly higher absolute levels of circulating endostatin compared with healthy controls (59,024 ± 2513 vs. 44,090 ± 1978 pg/mL, p&amp;lt;0.001). Multivariate-adjusted logistic regression analysis controlling for age, sex, minimum systolic and minimum diastolic BP during tilt, identified endostatin as an independent determinant for OH (beta-coefficient 0.80, p=0.025). The obtained area under the curve was 0.70, P&amp;lt;0.001, Figure). Conclusions Our findings indicate that patients with orthostatic hypotension have increased circulating levels of endostatin, independent of age, sex, and hemodynamic variables. Our results highlight the relevance of investigating the molecular pathways related to orthostatic hypotension. Further studies are warranted to assess the prognostic and therapeutic role of endostatin assessment in individuals with orthostatic hypotension.Tablestudy characteristicsFigureROC Curve

Effect of Diosmin on Selected Parameters of Oxygen Homeostasis.

Chronic venous disease (CVD) is a condition characterized by functional disturbances in the microcirculation of the superficial and deep veins, affecting up to 30% of the global population. Diosmin, a phlebotropic drug, is commonly used in the treatment of CVD, and its beneficial effects have been described in numerous clinical studies. However, the precise molecular mechanism underlying the activity of diosmin is not yet fully understood. Therefore, the objective of our study was to investigate whether diosmin has an impact on oxygen management, as cardiovascular diseases are often associated with hypoxia. In our study, patients were administered a daily dosage of 2 × 600 mg of diosmin for 3 months, and we evaluated several factors associated with oxygen management, angiogenesis, and inflammation using biochemical assays. Our findings indicate that diosmin reduced the levels of fibroblast growth factors (FGF) and vascular endothelial growth factor (VEGF-C), while increasing endostatin and angiostatin levels, suggesting a potential influence on angiogenesis regulation. Furthermore, diosmin exhibited anti-inflammatory properties by suppressing the levels of tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1β), and interleukin 6 (IL-6), while promoting the production of interleukin 12 (IL-12). Additionally, diosmin significantly decreased the levels of hypoxia-inducible factor (HIF), anion gap (AG), and lactate, indicating its potential influence on the hypoxia-inducible factor pathway. These findings suggest that diosmin may play a crucial role in modulating oxygen management and inflammation in the context of chronic venous disease.

Dan-Deng-Tong-Nao softgel capsule promotes angiogenesis of cerebral microvasculature to protect cerebral ischemia reperfusion injury via activating HIF-1α-VEGFA-Notch1 signaling pathway

BackgroundA proprietary Chinese herbal product called Dan-Deng-Tong-Nao softgel capsule (DDTNC) is used to treat ischemic stroke. However, the preventive mechanisms of DDTNC against cerebral ischemia reperfusion injury (CIRI) haven not been characterized. ObjectiveTo explore the mechanisms of protective effects of DDTNC against CIRI from both internal and external levels. MethodsChemical characterization was performed using UPLC. The potential protective mechanisms of DDTNC against CIRI were predicted using network pharmacology. Model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established in rats. An model of brain microvascular endothelial cells (BMECs) induced by oxygen-glucose deprivation/reoxygenation (OGD/R) was also established. We evaluated neurological deficits, cerebral infarct volume, cortical neuron damage, and mitochondrial swelling in vivo. We evaluated the expression of VEGFR2, VEGFA, HIF-1α, CD31, and CD34 in ischemic cortex, and VEGF, bFGF, BDNF, angiostatin, and endostatin in serum of rats and in BMEC supernatants. We also evaluated cell viability, cytotoxicity, intracellular ROS, apoptosis, and migration ability in vitro. ResultsSeven components were detected in DDTNC. KEGG enrichment analysis showed that DDTNC may modulate angiogenesis via the HIF-1 signaling pathway. DDTNC treatment reduced neurological score and infarct volume, and improved cell morphology of damaged neurons. Transmission electron microscopy showed that DDTNC reduced mitochondria swelling in cortical neurons. Furthermore, DDTNC reduced intracellular ROS and inhibited apoptosis. DDTNC boosted the expression of CD31, CD34, VEGFR2, VEGFA and HIF-1α, highlighting its involvement in angiogenesis, according to immunofluorescence studies. Furthermore, DDTNC enhanced tube formation and migration of BMECs in vitro. ELISA and western blotting indicated that DDTNCCSF induced the expression of VEGF, BDNF and bFGF, reduced the level of angiostatin and endostatin, increased the protein expression of VEGFA, Notch1 and HIF-1α in vitro and in vivo. ConclusionsDDTNC promoted angiogenesis to protect brain tissue against MCAO/R, and exerted protective effects against OGD/R in BMECs via activating HIF-1α-VEGFA-NOTCH1 signal transduction pathway.

Effect of Eight Weeks of Endurance Training on the Protein Levels of Some Angiogenesis Indicators in the Cardiac Tissue of Rats with Morphine Withdrawal Syndrome

Background: Exercise is a therapeutic procedure for addicts; however, its physiological mechanisms are not well understood. This study aimed to investigate the effect of eight weeks of endurance training on the levels of vascular endothelial growth factor and endostatin in the heart tissue of male rats with morphine withdrawal syndrome. Materials and Methods: This experimental study was conducted on 32 male rats randomly divided into four groups of eight: healthy control (HC), endurance training (ET), morphine control (CM), and morphine+endurance training (M.ET). Two morphine withdrawal groups were addicted to 0.4 mg/ml morphine sulfate for 21 days. The exercise groups performed eight weeks of treadmill running. At the end of the study, all rats were killed, and their heart tissue was removed. Protein levels of the indicators in this study were measured by ELISA kits. The data were analyzed by Tukey’s one-way ANOVA test. Results: The results of this study showed a significant decrease in VEGF levels (P&lt;0.001) and a significant increase in ES (P&lt;0.001) in the MC, compared to the HC. In addition, the increase in VEGF levels (P=0.014) and the decrease in ES (P=0.026) in the M.ET showed a significant difference, compared to the MC. Conclusion: Endurance training may be useful in preventing negative changes in angiogenesis and metabolic parameters related to morphine, which should be considered in the rehabilitation of addicts.

Basement membrane product, endostatin, as a link between inflammation, coagulation and vascular permeability in COVID-19 and non-COVID-19 acute respiratory distress syndrome.

Immune cell recruitment, endothelial cell barrier disruption, and platelet activation are hallmarks of lung injuries caused by COVID-19 or other insults which can result in acute respiratory distress syndrome (ARDS). Basement membrane (BM) disruption is commonly observed in ARDS, however, the role of newly generated bioactive BM fragments is mostly unknown. Here, we investigate the role of endostatin, a fragment of the BM protein collagen XVIIIα1, on ARDS associated cellular functions such as neutrophil recruitment, endothelial cell barrier integrity, and platelet aggregation in vitro. In our study we analyzed endostatin in plasma and post-mortem lung specimens of patients with COVID-19 and non-COVID-19 ARDS. Functionally, we investigated the effect of endostatin on neutrophil activation and migration, platelet aggregation, and endothelial barrier function in vitro. Additionally, we performed correlation analysis for endostatin and other critical plasma parameters. We observed increased plasma levels of endostatin in our COVID-19 and non-COVID-19 ARDS cohort. Immunohistochemical staining of ARDS lung sections depicted BM disruption, alongside immunoreactivity for endostatin in proximity to immune cells, endothelial cells, and fibrinous clots. Functionally, endostatin enhanced the activity of neutrophils, and platelets, and the thrombin-induced microvascular barrier disruption. Finally, we showed a positive correlation of endostatin with soluble disease markers VE-Cadherin, c-reactive protein (CRP), fibrinogen, and interleukin (IL)-6 in our COVID-19 cohort. The cumulative effects of endostatin on propagating neutrophil chemotaxis, platelet aggregation, and endothelial cell barrier disruption may suggest endostatin as a link between those cellular events in ARDS pathology.

Increased plasma endostatin and GDF15 in indolent non-Hodgkin lymphoma.

Increased microvascular density correlates with more advanced disease and unfavorable overall survival in non-Hodgkin lymphoma (NHL), suggesting that angiogenesis is important for disease progression. However, studies of anti-angiogenic agents in NHL patients, have generally not shown favorable outcomes. The aim of this study was to investigate whether plasma levels of a subset of angiogenesis-associated proteins are increased in indolent B-cell derived NHL (B-NHL) and to investigate whether the levels differ between patients with asymptomatic versus symptomatic disease. Plasma levels of growth differentiation factor 15 (GDF15), endostatin, matrix metalloproteinase 9 (MMP9), neutrophil gelatinase-associated lipocalin (NGAL), long pentraxin 3 (PTX3), and galectin 3 (GAL-3) were measured by ELISA in 35 patients with symptomatic indolent B-NHL, 41 patients with asymptomatic disease, and 62 healthy controls. Bootstrap t-tests were used to assess the relative differences in biomarker levels between groups. Group differences were visualized using a principal component plot. Mean plasma endostatin and GDF15 levels were significantly higher in symptomatic and asymptomatic lymphoma patients than in controls. Symptomatic patients had higher mean MMP9 and NGAL than controls. The finding of increased plasma endostatin and GDF15 in patients with asymptomatic indolent B-NHL suggests that increased angiogenic activity is an early event in indolent B-NHL disease progression.

Evaluation of Endothelial Progenitor Cell Characteristics as Clinical Biomarkers for Elderly Patients with Ischaemic Stroke.

Ageing impairs endothelial function and predisposes the person to ischaemic stroke (IS). Endothelial progenitor cells (EPCs) repair endothelial damage and induce post-ischaemic neovascularisation. Given the prevalence of IS in older population, this study explored whether changes in EPC number and function may reliably predict the type or outcome of stroke in patients ≥ 65years of age. For this, blood samples were collected once from healthy volunteers (HVs, n = 40) and four times (admission and days 7, 30 and 90 post-stroke) from participants with lacunar (n = 38) or cortical (n = 43) stroke. EPCs were counted with flow cytometry and defined as non-haematopoietic cells (CD45-) expressing markers for stemness (CD34 +), immaturity (CD133 +) and endothelial maturity (KDR +). Clonogenesis, tubulogenesis, migration and proliferation assays were performed as measures of EPC functionality. Biochemical profile of plasma inflammatory and angiogenic agents were studied using specific ELISAs. Primary outcome was disability or dependence on day 90 post-stroke, assessed by the modified Rankin Scale (mRS). Compared to HVs, EPC numbers were higher in stroke patients at all time points studied, reaching significance at baseline and day 30. No differences in EPC counts and functionality were observed between lacunar and cortical stroke groups at any time. Plasma endostatin, PDGF-BB, TNF-α and VEGF levels were higher in stroke patients vs HVs. Patient outcome, evaluated by mRS on day 90 post-stroke, did not correlate with EPC count or functionality. Baseline EPC counts may serve as a diagnostic marker for stroke but fail to distinguish between different stroke subtypes and predict post-stroke outcome.

Can endocan serve as a molecular “hepatostat” in liver regeneration?

BackgroundIntriguingly, liver regeneration after injury does not induce uncontrolled growth and the underlying mechanisms of such a “hepatostat” are still not clear. Endocan, a proteoglycan, was implicated in liver regeneration. It can support the function of hepatocyte growth factor/scatter factor in tissue repair after injury. Endostatin, a 20 kDa C-terminal fragment of collagen XVIII, may modulate the cessation of liver regeneration. eEF2K, a protein kinase that regulates protein synthesis, can regulate angiogenesis. Thus, we investigated the role of endocan, endostatin and eEF2K during normal liver regeneration.MethodsSerum samples and regenerating remnant liver tissues were obtained on various days after partial hepatectomy in rats. mRNA expression levels of Vegf and Pcna were analyzed in addition to immunohistochemical evaluations. Liver tissue protein levels of endostatin, endocan and p-eEF2K/eEF2K were determined with Western blot. Serum levels of endostatin and endocan were assessed with ELISA.ResultsPcna expression level in residual liver tissues peaked on day-1, while Vegf expression reached its highest level on days 1–3 after partial hepatectomy (70%). Endocan activity declined gradually on days 1–7. The decrease in liver endocan expression was accompanied by an increase in serum endocan levels. Partial hepatectomy induced a rapid increase in liver endostatin levels. Following its surge on day-1, endostatin expression gradually declined, which was accompanied by a peak in serum endostatin. Finally, partial hepatectomy was shown to regulate eEF2K; thus, increasing protein translation.ConclusionsWe revealed possible mechanistic insights into liver regeneration by examining the associations of Pcna, Vegf, endocan, endostatin, eEF2K with hepatic regeneration after partial hepatectomy. Indeed, endocan might serve as a useful biomarker to monitor clinical prognosis in a plethora of conditions such as recovery of donor’s remaining liver after living-donor liver transplant. Whether endocan might represent a strategy to optimize liver regeneration when given therapeutically needs to be investigated in future studies.

Endostatin level in coronavirus patients: a prospective study

Background Endostatin is a protein linked to the C-terminal of collagen in the basement membrane of endothelial cells. It functions as an antiangiogenic protein. It inhibits endothelial proliferation, migration, and tube formation. Studies have observed that it downregulates endothelial-signaling pathways of proangiogenic activity as well as upregulates the angiogenic gene. Aim This work was designated to explore the levels of endostatin in coronavirus disease 2019, trying to investigate its role as a prognostic marker. Patients and methods Patients with positive PCR for SARS-CoV-2 were divided into two groups (survivors and nonsurvivors). Computed tomography chest was for each patient. The nonsurvivor group comprised 19 patients and the survivor group had 31 patients. In addition, 50 normal volunteers participated in this study and served as a control group. Serum endostatin was measured by ELISA and was compared with other measured laboratory parameters. Results Endostatin was statically increased in nonsurvivors than both survivors and normal volunteers (P 1=0.007, P 2=&lt;0.001). However, this significant increase was still observed in survivors on comparing with normal individuals. There was a correlation between endostatin and different parameters in coronavirus disease 2019 patients. Conclusion The high level of endostatin in this prospective study and its correlation with laboratory makers and clinical manifestations leads us to consider it as a valuable prognostic factor. Moreover, it can predict mortality and severity of patients. It was important to conduct a study on large scale to confirm this value.

High Tumor Levels of Ki-67, VEGF and Endostatin Are Associated with Progression of Breast Cancer in Iraqi Women

High Tumor Levels of Ki-67, VEGF and Endostatin Are Associated with Progression of Breast Cancer in Iraqi Women