Vascular Endothelial Growth Factor (VEGF) and Neopterin Levels in Children with Steroid-sensitive and Steroid-resistant Nephrotic Syndrome.

BACKGROUND: The most common glomerular disease in children is nephrotic syndrome. Steroid-resistant nephrotic syndrome tends to have a worse disease course, which bears a significant risk of chronic kidney disease in children. OBJECTIVE: To compare VEGF and neopterin levels between children with steroid-sensitive nephrotic syndrome (SSNS), steroid-resistant nephrotic syndrome (SRNS), and also healthy (control) children. METHODS: This cross-sectional study was conducted at H. Adam Malik General Hospital, Indonesia from January to December 2018. There were 160 children aged 1 to 8 years with confirmed nephrotic syndrome and without end-stage renal disease and systemic diseases, divided into SSNS, SRNS, and control groups. Data regarding age, gender, urine albumin creatinine ratio (UACR), serum albumin, total cholesterol, urea, creatinine, VEGF, and neopterin levels were collected. A p-value of less than 0.05 is considered statistically significant. RESULTS: There were no differences between groups in gender (p = 0.269) and age (p = 0.375), but there was significant difference of UACR, albumin level, total cholesterol level, and VEGF level between groups, (all p< 0.001). There was a moderate positive correlation between VEGF level and UACR (r(158) = 0.439, p< 0.001) and a moderate negative correlation between neopterin level and albumin level (r(158)= -0.312, p = 0.005). CONCLUSION: There were no differences in serum VEGF and neopterin levels between steroid-sensitive and steroid-resistant nephrotic syndrome groups. Serum VEGF level was positively correlated with UACR while serum neopterin level was negatively correlated with serum albumin level.

Vascular endothelial growth factors and angiopoietins as new players in mastocytosis.

Mastocytosis is a disorder characterized by the abnormal proliferation and/or accumulation of mast cells in different organs. More than 90% of patients with systemic mastocytosis have a gain-of-function mutation in codon 816 of the KIT receptor on mast cells (MCs). The symptoms of mastocytosis patients are related to the MC-derived mediators that exert local and distant effects. MCs produce angiogenic and lymphangiogenic factors, including vascular endothelial growth factors (VEGFs) and angiopoietins (ANGPTs). Serum concentrations of VEGF-A, VEGF-C, VEGF-D, ANGPT1 and ANGPT2 were determined in 64 mastocytosis patients and 64 healthy controls. Intracellular concentrations and spontaneous release of these mediators were evaluated in the mast cell lines ROSAKIT WT and ROSA KIT D816V and in human lung mast cells (HLMCs). VEGF-A, ANGPT1, ANGPT2 and VEGF-C concentrations were higher in mastocytosis patients compared to controls. The VEGF-A, ANGPT2 and VEGF-C concentrations were correlated with the symptom severity. ANGPT1 concentrations were increased in all patients compared to controls. ANGPT2 levels were correlated with severity of clinical variants and with tryptase levels. VEGF-A, ANGPT1 and VEGF-C did not differ between indolent and advanced mastocytosis. ROSAKIT WT, ROSAKIT D816V and HLMCs contained and spontaneously released VEGFs and ANGPTs. Serum concentrations of VEGFs and ANGPTs are altered in mastocytosis patients.

The expression and significance of leukemia inhibitory factor, interleukin-6 and vascular endothelial growth factor in Chinese patients with endometriosis.

OBJECTIVE: To observe the levels of leukemia inhibitory factor (LIF), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in blood, peritoneal fluid, ectopic endometrial tissue, and ectopic endometrial stromal cells of patients with endometriosis, and to compare expression of IL-6, LIF and VEGF expression between endometriotic and non-endometriotic patients underwent laparoscopic surgery. METHODS: Thirty-one patients who underwent laparoscopic surgery for endometriosis in our hospital from January 2018 to January 2020 were included in the observation group, and 32 patients who underwent laparoscopic surgery for uterine fibroids, ovarian serous cystadenoma, and ovarian teratomas, were included in the control group. The levels of LIF, IL-6 and VEGF in the blood and peritoneal fluid of the two groups of patients were detected. The levels of LIF, IL-6 and VEGF in ectopic endometrial tissue and self-paired eutopic endometrial tissue, ectopic endometrial stromal cells and self-paired eutopic endometrial stromal cells of patients in the observation group were detected. After treating the primary cultured ectopic endometrial stromal cells with LIF and IL-6 alone or in combination, the changes of VEGF mRNA of ectopic endometrial stromal cells and the VEGF levels in the supernatant were observed. RESULTS: The levels of LIF, IL-6 and VEGF in the blood and peritoneal fluid of the observation group were all higher than those of the control group (P < 0.05), and the levels of LIF, IL-6 and VEGF in the peritoneal fluid of the observation group were significantly higher than those in the blood (P < 0.05). In the observation group, the expression levels of LIF-mRNA and IL-6 mRNA in the ectopic endometrial tissue were higher than those in the self-paired eutopic endometrial tissues (P < 0.05), while the expression level of VEGF mRNA in the ectopic endometrial tissues was lower than that in the self-paired eutopic endometrial tissues (P < 0.05). Besides, the mRNA expression levels of LIF, IL-6 and VEGF in ectopic endometrial stromal cells of the observation group were all higher than those in the self-paired eutopic endometrial stromal cells (P < 0.05). After stimulating ectopic endometrial stromal cells with LIF, IL-6 and LIF + IL-6, respectively, the VEGF levels in the supernatant were all significantly higher than that in the blank control group (P < 0.05). CONCLUSION: The LIF, IL-6 and VEGF levels in blood and peritoneal fluid were increased in patients with endometriosis, and increased LIF and IL-6 in ectopic endometriosis stromal cells can play a synergistic role in increasing the VEGF levels, which may be involved in the occurrence and development of endometriosis.

Clearance of inflammatory cytokines in patients with septic acute kidney injury during renal replacement therapy using the EMiC2 filter (Clic-AKI study).

BACKGROUND: The EMiC2 membrane is a medium cut-off haemofilter (45 kiloDalton). Little is known regarding its efficacy in eliminating medium-sized cytokines in sepsis. This study aimed to explore the effects of continuous veno-venous haemodialysis (CVVHD) using the EMiC2 filter on cytokine clearance. METHODS: This was a prospective observational study conducted in critically ill patients with sepsis and acute kidney injury requiring kidney replacement therapy. We measured concentrations of 12 cytokines [Interleukin (IL) IL-1ß, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, vascular endothelial growth factor, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF)] in plasma at baseline (T0) and pre- and post-dialyzer at 1, 6, 24, and 48 h after CVVHD initiation and in the effluent fluid at corresponding time points. Outcomes were the effluent and adsorptive clearance rates, mass balances, and changes in serial serum concentrations. RESULTS: Twelve patients were included in the final analysis. All cytokines except EGF concentrations declined over 48 h (p < 0.001). The effluent clearance rates were variable and ranged from negligible values for IL-2, IFN-γ, IL-1α, IL-1ß, and EGF, to 19.0 ml/min for TNF-α. Negative or minimal adsorption was observed. The effluent and adsorptive clearance rates remained steady over time. The percentage of cytokine removal was low for most cytokines throughout the 48-h period. CONCLUSION: EMiC2-CVVHD achieved modest removal of most cytokines and demonstrated small to no adsorptive capacity despite a decline in plasma cytokine concentrations. This suggests that changes in plasma cytokine concentrations may not be solely influenced by extracorporeal removal. TRIAL REGISTRATION: NCT03231748, registered on 27th July 2017.

Correlations of recurrence of gastric cancer in patients after radical surgery with serum gastrointestinal hormones, vascular endothelial growth factors and serum anti-helicobacter pylori IgG antibody.

PURPOSE: To study the correlations of the recurrence of gastric cancer in patients after radical surgery with serum gastrointestinal hormones, serum anti-Helicobacter pylori (anti-HP) immunoglobulin G (IgG) antibody and vascular endothelial growth factors (VEGFs). METHODS: According to whether gastric cancer recurred within five years after surgery, the patients were divided into recurrence group (RE group, gastric cancer recurred within five years after surgery, n=78) and non-recurrence group (NR group, gastric cancer did not recur within five years after surgery, n=69). Differences in lymph node metastasis, gastrointestinal hormones, VEGFs, anti-HP IgG antibody and the tumor-node-metastasis (TNM) stage between RE group and NR group were detected and compared, so as to analyze the correlations of these factors with the recurrence of gastric cancer in patients after radical surgery. RESULTS: The levels of gastrin (GAS) and motilin (MTL) after meals in RE group and NR group were slightly higher than those before meals. The levels of GAS and MTL in RE group were higher than those in NR group in the two periods (p<0.05). Besides, compared with NR group, RE group had lower pepsinogen (PG) I, PG II and PG I/II ratio (PGR), but a higher positive value of anti-HP IgG antibody (p<0.05) and higher levels of VEGF-A, VEGF-C and VEGF-D (p<0.05). Moreover, there were markedly more cases of gastric cancer in stage III, remarkably few cases of gastric cancer in stage I and obviously more cases of lymph node metastasis in RE group than those in NR group (p<0.05). Multivariate analysis showed that gastrointestinal hormones, lymph node metastasis, VEGFs, the TNM stage of gastric cancer and anti-HP IgG antibody were all risk factors for the recurrence of gastric cancer after radical surgery (p<0.05). CONCLUSIONS: The recurrence of gastric cancer in patients after radical surgery is related to the TNM stage of gastric cancer, gastrointestinal hormones, VEGFs, lymph node metastasis, anti-HP IgG antibody and other factors.

Significance of vascular endothelium growth factor testing in exhaled breath condensate of patients with acute respiratory distress syndrome.

OBJECTIVE: We aimed to observe and investigate the clinical significance of vascular endothelium growth factor (VEGF) levels in exhaled breath condensate (EBC) from patients with acute respiratory distress syndrome (ARDS). METHODS: An improved EcoScreen condenser was used to collect EBC from 31 ARDS patients on mechanical ventilation and from 22 healthy subjects. Serum and EBC VEGF levels were analyzed with ELISA. VEGF levels in the EBC of patients with different grades of lung injuries were analyzed. The correlation between VEGF levels and clinical indicators was analyzed. RESULTS: Serum and EBC VEGF levels were linearly and positively correlated with a correlation coefficient of 0.694 (P< 0.01). The VEGF level in the EBC of ARDS patients was significantly lower than that in the control group (P< 0.01). The VEGF level in the EBC of the mild ARDS group was higher than that in the moderate-severe ARDS group (P< 0.01). The VEGF level in the EBC of the survival group was higher than that in the mortality group. The VEGF level in the EBC of ARDS patients was positively correlated with PaO2/FiO2 and PaO2 and was negatively correlated with lung injury score (LIS) and A-aDO2/PaO2. CONCLUSION: The changes in VEGF levels in the EBC of ARDS patients can Respiratory Medicine, reflect the severity of lung injury. Therefore, VEGF level in EBC can be used as an auxiliary index for judging the severity and prognosis of ARDS patients.

Association of disease condition with changes in intestinal flora, and plasma endotoxin and vascular endothelial growth factor levels in patients with liver cancer.

OBJECTIVE: Currently, the therapeutic effect on patients with liver cancer is associated with disease development. Meanwhile, the efficacy in patients with advanced liver cancer is far from satisfactory. Therefore, the aim of this study was to explore the association of disease condition with changes in liver function indexes, intestinal flora, and plasma endotoxin (ET) and vascular endothelial growth factor (VEGF) levels in patients with liver cancer. PATIENTS AND METHODS: A total of 300 patients with primary liver cancer in our hospital were enrolled in this study. All patients were divided into three groups, including early liver cancer group, middle liver cancer group, and advanced liver cancer group. Peripheral blood was collected from each subject to detect liver function indexes, procalcitonin (PCT), plasma ET, and VEGF levels. Furthermore, mid-posterior-segment stools were collected from 15 cases in each group, and sent to the company for detection of intestinal flora. RESULTS: Liver function indexes in peripheral blood of patients with liver cancer changed with the changes in disease condition. With the progression of liver cancer, the level of aspartate aminotransferase (AST) increased significantly, and the highest was observed in advanced liver cancer patients [(91.18±10.34) U/L] (p=0.046). However, the level of plasma total protein declined significantly, which was (24.83±1.75) g/L in advanced liver cancer patients (p=0.035). The changes in total bilirubin were significantly associated with the progression of liver cancer (p=0.003). The abundance of Clostridiales, Firmicutes, and Streptococcus in the intestinal tract was high in early liver cancer group. The abundance of Ruminococcaceae, Pasteurellaceae, Tanticharoenia, and Vagococcus in the intestinal tract was high in middle liver cancer group. Meanwhile, the abundance of Bifidobacteriales, Actinobacteria, Barnesiella, Porphyromonadaceae, and Pseudomonadales in the intestinal tract was high in advanced liver cancer group. In patients with liver cancer, the level of Enterobacteriaceae was positively correlated with that of Firmicutes (r=0.36, p=0.003), whereas it was negatively correlated with Lactobacillus (r=-0.72, p=0.021). The level of Lactobacillus was positively correlated with that of Ruminococcaceae (r=0.39, p=0.043), whereas it was negatively correlated with that of Firmicutes (r=-0.27, p=0.019). In addition, the level of PCT markedly rose in advanced liver cancer group [(6.89±0.35) ng/mL] (p=0.021). The level of ET increased significantly with the development of liver cancer, with the highest level observed in advanced liver cancer group [(0.71±0.09) EU/mL] (p=0.004). The level of VEGF also increased remarkably with the aggravation of liver cancer, and the highest was found in advanced liver cancer group [(112.33±2.11) µmol/L], showing differences among groups (p<0.05). CONCLUSIONS: With the progression of liver cancer, the abundance of Barnesiella, etc., rose and that of Ruminococcaceae, etc., declined in the intestinal tract. Meanwhile, the composition of intestinal flora was changed, and the levels of plasma ET and VEGF increased.

Placenta accreta spectrum: biomarker discovery using plasma proteomics.

BACKGROUND: Many cases of placenta accreta spectrum are not diagnosed antenatally, despite identified risk factors and improved imaging methods. Identification of plasma protein biomarkers could further improve the antenatal diagnosis of placenta accreta spectrum . OBJECTIVE: The purpose of this study was to determine if women with placenta accreta spectrum have a distinct plasma protein profile compared with control subjects. STUDY DESIGN: We obtained plasma samples before delivery from 16 participants with placenta accreta spectrum and 10 control subjects with similar gestational ages (35.1 vs 35.5 weeks gestation, respectively). We analyzed plasma samples with an aptamer-based proteomics platform for alterations in 1305 unique proteins. Heat maps of the most differentially expressed proteins (T test, P<.01) were generated with matrix visualization and analysis software. Principal component analysis was performed with the use of all 1305 proteins and the top 21 dysregulated proteins. We then confirmed dysregulated proteins using enzyme-linked immunosorbent assay and report significant differences between placenta accreta spectrum and control cases (Wilcoxon-rank sum test, P<.05). RESULTS: Many of the top 50 proteins that significantly dysregulated in participants with placenta accreta spectrum were inflammatory cytokines, factors that regulate vascular remodeling, and extracellular matrix proteins that regulate invasion. Placenta accreta spectrum, with the use of the top 21 proteins, distinctly separated the placenta accreta spectrum cases from control cases (P<.01). Using enzyme-linked immunosorbent assay, we confirmed 4 proteins that were dysregulated in placenta accreta spectrum compared with control cases: median antithrombin III concentrations (240.4 vs 150.3 mg/mL; P=.002), median plasminogen activator inhibitor 1 concentrations (4.1 vs 7.1 ng/mL; P<.001), soluble Tie2 (13.5 vs 10.4 ng/mL; P=.02), soluble vascular endothelial growth factor receptor 2 (9.0 vs 5.9 ng/mL; P=.003). CONCLUSION: Participants with placenta accreta spectrum had a unique and distinct plasma protein signature.

Sentinel biomarkers in HCV positive patients with mixed cryoglobulinemia.

BACKGROUND: Infections, autoimmunity and cancer play a role as determinants of etiology in Hepatitis C virus (HCV) related mixed cryoglobulinemia (MC). Several factors of risk have been suggested as markers of pathogenesis and progression of HCV-related MC into B cell Non-Hodgkin's Lymphoma (B-NHL). Here, we evaluated IgG subclass distribution, free light chains (FLCs) and vascular endothelial growth factor (VEGF) as a new combination of biomarkers. METHODS: We measured IgG1-4 subclasses, FLCs and VEGF levels in sera 53 from HCV-related MC, in comparison with 40 sera from HCV negative patients with rheumatoid arthritis (RA) and 30 from healthy blood donors (HBD). RESULTS: IgG3 levels were significantly higher in HCV-MC patients with a decrement of IgG2 and IgG4; FLC levels significantly increased in both MC and RA patients' groups; serological VEGF was higher in HCV-MC patients than in HBD in correlation with k and λ levels. CONCLUSION: Our results suggest that a specific IgG subclasses pattern together with raised levels of FLCs and VEGF could represent the biomarker "signature" of an inflammation multistage of acquired immune system.

Plasma biomarkers of astrocytic and neuronal dysfunction in early- and late-onset Alzheimer's disease.

INTRODUCTION: We investigated plasma proteomic markers of astrocytopathy, brain degeneration, plasticity, and inflammation in sporadic early-onset versus late-onset Alzheimer's disease (EOAD and LOAD). METHODS: Plasma was analyzed using ultra-sensitive immuno-based assays from 33 EOAD, 30 LOAD, and 36 functionally normal older adults. RESULTS: Principle component analyses identified 3 factors: trophic (BDNF, VEGF, TGFß), degenerative (GFAP, NfL), and inflammatory (TNFα, IL-6, IP-10, IL-10). Trophic factor was elevated in both AD groups and associated with cognition and gray matter volumes. Degenerative factor was elevated in EOAD, with higher levels associated with worse functioning in this group. Biomarkers of inflammation were not significantly different between groups and were only associated with age. DISUCSSION: Plasma proteomic biomarkers provide novel means of investigating molecular processes in vivo and their contributions to clinical outcomes. We present initial investigations of several of these fluid biomarkers, capturing aspects of astrocytopathy, neuronal injury, cellular plasticity, and inflammation in EOAD versus LOAD.

POEMS Syndrome Showing Left Ventricular Dysfunction and Extracellular Edema Assessed by Cardiac Magnetic Resonance Imaging.

Although cardiac involvement is rare in polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, the clinical course becomes considerably worse on complication with cardiac lesions. The increased release of various cytokines has been observed in the pathogenesis of POEMS syndrome, and serum vascular endothelial growth factor (VEGF) levels are known to be associated with the disease activity. We herein report a patient with POEMS syndrome who showed left ventricular systolic dysfunction and was treated with lenalidmide therapy. Of note, the reduction in extracellular edema in the left ventricular wall was clearly visualized by changes in the native T1 values and extracellular volumes on cardiac magnetic resonance imaging.

Nectin-2 in ovarian cancer: How is it expressed and what might be its functional role?

Nectin-2 is an adhesion molecule that has been reported to play a role in tumor growth, metastasis and tumor angiogenesis. Herein, we investigated Nectin-2 in ovarian cancer patients and in cell culture. Tumor as well as peritoneal biopsies of 60 ovarian cancer patients and 22 controls were dual stained for Nectin-2 and CD31 using immunohistochemistry. Gene expression of Nectin-2 was quantified by real-time PCR and differences analyzed in relation to various tumor characteristics. In the serum of patients, vascular endothelial growth factor (VEGF) was quantified by ELISA. Effect of VEGF on Nectin-2 expression as well as permeability was investigated in HUVEC. In tumor biopsies, Nectin-2 protein was mainly localized in tumor cells, whereas in peritoneal biopsies, clear colocalization was found in the vasculature. T3 patients had a significantly higher percentage of positive lymph nodes and this correlated with survival. Nectin-2 was significantly upregulated in tumor biopsies in patients with lymph node metastasis and with residual tumor >1 cm after surgery. Nectin-2 expression was significantly suppressed in the peritoneal endothelium of patients associated with significantly increased VEGF serum levels. In cell culture, VEGF stimulation led to a significant downregulation of Nectin-2 which was reversed by VEGF-inhibition. In addition, Nectin-2 knockdown in endothelial cells was associated with significantly increased endothelial permeability. Nectin-2 expression in ovarian cancer may support tumor cell adhesion, leading to growth and lymph node metastasis. In addition, VEGF-induced Nectin-2 suppression in peritoneal endothelium may support an increase in vascular permeability leading to ascites production.

Synchronous vascular endothelial growth factor protein profiles in both tissue and serum identify metastasis and poor survival in colorectal cancer.

Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. We examined if tumor tissue and circulating protein levels of all vascular endothelial growth factors (VEGFs) and VEGF receptors (VEGFRs) were synchronous and different in Taiwan patients with metastatic CRC (mCRC) vs. non-mCRC. We analyzed samples from 109 patients enrolled from 2005-2017, 50 with stages I/II and 59 with stages III/IV CRC. We found that VEGF-A, -B, -C, -D, placental growth factor (PlGF), VEGFR-1, VEGFR-2, and VEGFR-3 were higher in tumor tissues than non-tumor tissues. Metastatic patients had higher levels of circulating VEGFs and soluble VEGFRs (sVEGFRs) than healthy subjects, as well as higher VEGF-A, -B, -C, -D, and PlGF proteins in both tumor tissue and serum than non-metastatic patients. Protein levels of VEGF and VEGFR were mainly associated with the patient's age, tumor site, tumor size, tumor stage, and lymph node metastasis. Patients exhibiting high levels of VEGF, VEGFR, and sVEGFR had a shorter overall survival and disease-free survival than those with low levels. We conclude that synchronous changes in VEGF and VEGFR levels in CRC tissue and serum VEGF can discriminate between metastatic and non-metastatic subjects and high levels are associated with poor survival in CRC.

VEGF serum concentration and irreversible bronchoconstriction in adult asthmatics.

BACKGROUND: Vascular endothelial growth factor (VEGF) is an angiogenic, heparin-binding glycoprotein playing an important role in the pathogenesis of many diseases and disorders, including asthma. It has been reported that increased VEGF serum concentration is a biomarker of neovascularization, which could suggest that higher VEGF expression may be relevant to asthmatics with airway remodeling and irreversible bronchoconstriction. OBJECTIVES: The aim of this study was to assess the possible association between VEGF serum concentration and irreversible bronchoconstriction in adult patients with a diagnosis of asthma. MATERIAL AND METHODS: This study involved 82 adult patients with asthma (42 persons with and 40 persons without irreversible bronchoconstriction) and 40 healthy adult controls. Vascular endothelial growth factor serum concentration was analyzed using enzyme-linked immunosorbent assay (ELISA). RESULTS: Vascular endothelial growth factor serum concentration in patients with asthma was higher than in healthy controls (p = 0.0131), particularly in those from the subgroup of irreversible bronchoconstriction (p = 0.0133). The rising tendency was confirmed using the Kruskal­Wallis rank sum test that showed a significant difference (p = 0.0374) in VEGF values among the 3 groups examined: healthy controls (Me = 246.6 pg/mL), asthmatics with reversible bronchoconstriction (Me = 288.6 pg/mL) and asthmatics with irreversible bronchoconstriction (Me = 340.6 pg/mL). However, the direct comparison between the 2 asthmatics groups (reversible vs irreversible bronchoconstriction) did not show a statistically significant difference (p = 0.5521). CONCLUSIONS: Increased VEGF serum concentration is characteristic of patients with asthma, especially those with irreversible bronchoconstriction.

Dentin matrix protein 1 correlates with the severity of hemorrhagic fever with renal syndrome and promotes hyper-permeability of endothelial cells infected by Hantaan virus.

Hantaviruses are the major causative agents of hemorrhagic fever with renal syndrome (HFRS) in humans, which is characterized by increased capillary permeability. Dentin matrix protein 1 (DMP1) has been shown to degrade components of the basal membrane and interendothelial junctions via matrix metalloproteinase-9. To study the changes of serum DMP1 in HFRS, we determined the concentration of DMP1 using sandwich enzyme-linked immunosorbent assay. We found that serum DMP1 concentrations increased significantly, and reached peak value during the oliguric phase and in the critical group in HFRS patients. Moreover, serum DMP1 concentrations were closely related to blood urea nitrogen, creatinine, cystatin C, and vascular endothelial growth factor (VEGF). We further explored the role of DMP1 in HTNV-infected human umbilical vein endothelial cells (HUVECs) model. Data from immunocytochemistry showed that VEGF and tumor necrosis factor-α (TNF-α) promoted the expression of DMP1 on HTNV-infected HUVECs. Results from transwell assays demonstrated that the permeability of HUVECs increased significantly after HTNV infection with the addition of DMP1, VEGF, and TNF-α. This study suggests that elevated DMP1 concentrations may be associated with disease stage, severity, and the degree of acute kidney injury. DMP1 is involved in the regulation of capillary permeability in HFRS caused by hantavirus infection.

Research of stroke combined hyperlipidemia-induced erectile dysfunction in rat model.

Objective: The study was aimed to evaluate the influences of erectile dysfunction (ED) in a rat model of stroke combined with hyperlipidemia (HLP). Methods: Male Sprague-Dawley rats were divided into control and hyperlipidemia (HLP) groups. HLP model was constructed by feeding with high-fat and cholesterol diets. Serum levels of total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride (TG), and non-HDL were identified to check the model was success. Stroke model was established by FeCl3. ICP/MAP value was detected to evaluate the erectile function of rats. Serum level of lipoproteins and the expressions of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) were detected by ELISA. Hematoxylin-eosin (HE) staining of corpus cavernosum and measurement of penis length were utilized to assessment erectile function. Western blot was used. Results: TC, TG, LDL, and non-HDL-C in serum were up-regulated, while HDL level was attenuated. After treatment, the serum lipid level recovered. From the ICP/MAP values, the erectile function of both two treatment groups recovered. The expression of PDE5A was up-regulated, while the levels of eNOS and cGMP were suppressed after surgery. The length of penis was decreased, and corpus cavernosum was damaged following HLP and stroke. However, the erectile function was recovered after treatment. Conclusion: Stroke combined HLP caused ED through NO-cGMP-PDE5 pathway.

Vascular endothelial growth factor, endostatin levels and clinical features among patients with ulcerative colitis and irritable bowel syndrome and among healthy controls: a cross-sectional analytical study

ABSTRACT BACKGROUND: Increased angiogenetic activity in inflammatory bowel disease (IBD) has been shown in previous studies. The aim of this study was to evaluate the relationship of serum vascular endothelial growth factor (VEGF) and endostatin levels with clinical features and mucosal expression in patients with ulcerative colitis (UC). DESIGN AND SETTING: Cross-sectional analytical study conducted in a tertiary-level public hospital. METHODS: Serum VEGF and endostatin levels were determined in 82 individuals: 39 with UC, 28 with irritable bowel syndrome (IBS) and 15 healthy controls (HCs), using enzyme-linked immunosorbent assays (ELISA). VEGF and endostatin expressions were studied using immunohistochemistry (IHC). RESULTS: Mean serum VEGF and endostatin levels were significantly higher in patients with UC than in patients with IBS and in HCs (511.9 ± 377.5 pg/ml, 305.0 ± 121.42 pg/ml and 36.1 ± 40.6 pg/ml; P = 0.001 for VEGF; and 155.50 ± 59.8 ng/ml, 116.9 ± 23.8 ng/ml and 102.2 ± 22.4 ng/ml; P < 0.001 for endostatin, respectively). There was a positive correlation between serum VEGF and endostatin levels (r = 0.422; P < 0.01). Mean H-scores for VEGF expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma, endothelium and epithelium. Mean H-scores for endostatin expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma and endothelium. There was no endostatin expression in the epithelium. CONCLUSION: Increased endostatin appears to be a defensive reaction to increased VEGF in patients with UC.

Efecto del resveratrol sobre las concentraciones séricas del factor de crecimiento endotelial vascular durante la aterosclerosis / Effect of resveratrol on seric vascular endothelial growth factor concentrations during atherosclerosis

Introducción: El resveratrol tiene propiedades antiinflamatorias y antiaterogénicas; sin embargo, se desconoce su efecto sobre el factor de crecimiento endotelial vascular (VEGF) en la aterosclerosis. Objetivo: Evaluar el efecto del resveratrol sobre las concentraciones séricas del VEGF durante la progresión y evolución de la aterosclerosis y su evolución en el tiempo en conejos alimentados con dieta enriquecida con colesterol. Materiales y métodos: Cuarenta y ocho conejos machos divididos en cuatro grupos de 12 conejos recibieron: grupo 1 (control): conejarina; grupo 2: conejarina suplementada con 0,5% colesterol; grupo 3 (control resveratrol): conejarina y resveratrol (2 mg/kg); grupo 4: conejarina suplementada con 0,5% colesterol y resveratrol, durante 12 semanas. Se realizaron determinaciones séricas de triglicéridos, colesterol y sus fracciones, VEGF y proteína C reactiva (PCR) al inicio, a la 6.a y a la 12.a semana de experimentación. La mitad de los conejos fueron sacrificados a la 6.a y a la 12.a semana y se realizó estudio histológico de su aorta. Resultados: El VEGF y la PCR aumentaron en los grupos2 y 4 desde la 6.a semana de experimentación con respecto a los grupos 1 y 3, respectivamente (p < 0,001). En la duodécima semana se observó una disminución de los niveles de VEGF y PCR en el grupo 4 con respecto al grupo 2 (p < 0,004). El tratamiento con resveratrol disminuyó la formación de ateromas. Conclusiones: El VEGF y la PCR séricos constituyen marcadores tempranos no invasivos de inflamación y aterosclerosis. La suplementación oral de resveratrol ejerce efectos antiinflamatorios y antiateroscleróticos, disminuyendo las concentraciones séricas de VEGF y PCR, y la formación y evolución de las lesiones ateroscleróticas

Introduction: Although it is known that resveratrol has anti-inflammatory and anti-atherogenic actions, its effect on vascular endothelial growth factor (VEGF) in atherosclerosis is unknown. Objective: To evaluate the effect of resveratrol on serum concentrations of VEGF during the progression and evolution of atherosclerosis, as well as and its evolution over time in rabbits fed with a cholesterol diet. Materials and methods: A total of 48 New Zealand white male rabbits were randomly divided into four groups of 12 rabbits: group 1 (control): standard diet (commercial rabbit food); group 2: cholesterol diet (0.5% cholesterol); group 3 (control resveratrol): standard diet (commercial rabbit food) and resveratrol (2 mg/Kg); group 4: cholesterol diet (0.5% cholesterol) and resveratrol (2 mg/Kg), for 12 weeks. Blood samples of overnight-fasted rabbits were collected at baseline and the sixth and twelfth weeks, and the lipid profile, VEGF, and C-reactive protein (CRP) levels were determined. Half of the animals were sacrificed on the sixth or twelfth week, and the aorta was dissected for histological studies. Results: VEGF and CRP levels were significantly higher in groups 2 and 4 than in groups1 and 3, respectively, from the 6th week (p < 0.001). VEGF and CRP were significantly lower in group 4 than in group 2 on 12 th week (p < 0.004). Supplementation of resveratrol reduced the formation of atherosclerotic lesions. Conclusions: Serum VEGF and CRP levels are early markers of atherosclerosis. Oral supplementation of resveratrol exerts anti-inflammatory and anti-atherosclerotic effects, decreasing serum concentrations of VEGF and CRP and the formation and evolution of atherosclerotic lesions

Tuberculous lymphadenitis is associated with altered levels of circulating angiogenic factors.

BACKGROUND: Angiogenic factors are important in granuloma formation and serve as biomarkers in pulmonary tuberculosis (PTB). The relationship between these markers and tuberculous lymphadenitis (TBL) is not known. OBJECTIVE AND DESIGN: To examine the association of vascular endothelial growth factor (VEGF) and angiopoietin (Ang) family molecules in TBL, we measured systemic levels of VEGF-A, C, D, R1 (VEGF-receptor 1), R2, R3, Ang-1, Ang-2 and TIE2 (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2) levels in TBL, latent tuberculous infection (LTBI) and lymph node culture supernatants (VEGF-A, C and Ang-2) of the same TBL patients. RESULTS: Circulating levels of VEGF-A and VEGF-C were significantly diminished, whereas VEGF-R2, R3, Ang-2 and TIE2 levels were significantly increased, in TBL. Likewise, VEGF-A, C and Ang-2 levels were significantly increased in lymph node supernatants compared with plasma in individuals with TBL. Receiver operating characteristic curve analysis showed that VEGF-C and VEGF-R2 markers clearly distinguished TBL from LTBI. Following treatment, VEGF-C and Ang-1 levels were significantly altered. No association was observed between angiogenic factors and culture grade or lymph node size, except for VEGF-A. VEGF-A was also significantly decreased in multiple lymph nodes compared with single lymph nodes. CONCLUSIONS: Our data suggest that altered levels of circulating angiogenic factors in TBL might reflect underlying vasculo-endothelial dysfunction. Reversal of angiogenic markers after anti-tuberculosis treatment suggests that these angiogenic markers may serve as biomarkers of disease severity or response to treatment in TBL.

Correlation between increasing tissue ischemia and circulating levels of angiogenic growth factors in peripheral artery disease.

INTRODUCTION: The aim of the present study was to assess the circulating levels of vascular endothelial growth factor (VEGF) and other suggested therapeutic growth factors with the degree of ischemia in patients with different clinical manifestations of peripheral arterial disease (PAD) according to the Rutherford grades. METHODS: The study cohort consists of 226 consecutive patients admitted to a Department of Vascular Surgery for elective invasive procedures. PAD patients were grouped according to the Rutherford grades after a clinical assessment. Ankle-brachial pressure indices (ABI) and absolute toe pressure (TP) values were measured. Serum levels of circulating VEGF, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF) were measured from serum and analysed against Rutherford grades and peripheral hemodynamic measurements. RESULTS: The levels of VEGF (P = 0.009) and HGF (P < 0.001) increased significantly as the ischaemic burden became more severe according to the Rutherford grades. PDGF behaved in opposite manner and declined along increasing Rutherford grades (P = 0.004). A significant, inverse correlations between Rutherford grades was detected as follows; VEGF (Pearson's correlation = 0.183, P = 0.004), HGF (Pearson's correlation = 0.253, P < 0.001), bFGF (Pearson's correlation = 0.169, P = 0.008) and PDGF (Pearson's correlation = 0.296, P < 0.001). In addition, VEGF had a clear direct negative correlation with ABI (Pearson's correlation -0.19, P = 0.009) and TP (Pearson's correlation -0.20, P = 0.005) measurements. CONCLUSIONS: Our present observations show that the circulating levels of VEGF and other suggested therapeutic growth factors are significantly increased along with increasing ischemia. These findings present a new perspective to anticipated positive effects of gene therapies utilizing VEGF, HGF, and bFGF, because the levels of these growth factors are endogenously high in end-stage PAD.