VEGFA165 can rescue excess steroid secretion, inflammatory markers and follicle arrest in the ovarian cortex of high A4 cows

2021 ◽  
Author(s):  
Mohamed A Abedal-Majed ◽  
Shelby A Springman ◽  
Courtney M Sutton ◽  
Alexandria P Snider ◽  
Brooke E Bell ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Early Stage ◽  
Vascular Endothelial ◽  
Steroid Secretion ◽  
Cell Dysfunction ◽  
Ovarian Cortex ◽  
Calving Rate ◽  
Early Primary ◽  
And Control ◽  
Endothelial Growth Factor

Abstract A population of cows with excess androstenedione (A4; High A4) in follicular fluid, with follicular arrest, granulosa cell dysfunction, and a 17% reduction in calving rate was previously identified. We hypothesized that excess A4 in the ovarian microenvironment caused the follicular arrest in High A4 cows and Vascular Endothelial Growth Factor A (VEGFA) would rescue the High A4 phenotype. In trial 1, prior to culture, High A4 ovarian cortex (n = 9) had greater numbers of early stage follicles (primordial) and fewer later stage follicles compared to Controls (n = 11). Culture for 7 days did not relieve this follicular arrest; instead, High A4 ovarian cortex had increased indicators of inflammation, Anti-Mullerian Hormone (AMH) and A4 secretion compared to Controls. In trial 2, we tested if VEGFA isoforms could rescue the High A4 phenotype. High A4 (n = 5) and Control (n = 5) ovarian cortex was cultured with: 1) PBS; 2) VEGFA165 (50 ng/ml); 3) VEGFA165B (50 ng/ml); or 4) VEGFA165 + VEGFA165B (50 ng/ml each) for 7 days. Follicular progression increased with VEGFA165 in High A4 cows with greater early primary, primary, and secondary follicles than Controls. Similar to trial 1, High A4 ovarian cortex secreted greater concentrations of A4 and other steroids, and had greater indicators of inflammation compared to Controls. However, VEGFA165 rescued steroidogenesis, oxidative stress, and fibrosis. VEGFA165 and VEGFA165b both reduced IL-13, INFα, and INFβ secretion in High A4 cows to control levels. Thus, VEGFA165 may be a potential therapeutic to restore the ovarian steroidogenic microenvironment and promote folliculogenesis.

scholarly journals Porcine ovarian cortex-derived putative stem cells can differentiate into endothelial cells in vitro

2021 ◽  
Author(s):  
Kamil Wartalski ◽  
Gabriela Gorczyca ◽  
Jerzy Wiater ◽  
Zbigniew Tabarowski ◽  
Małgorzata Duda
Keyword(s):  
Stem Cells ◽  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Primary Component ◽  
Marker Genes ◽  
Vascular Endothelial ◽  
Ovarian Cortex ◽  
Endothelial Growth Factor

AbstractEndothelial cells (ECs), the primary component of the vasculature, play a crucial role in neovascularization. However, the number of endogenous ECs is inadequate for both experimental purposes and clinical applications. Porcine ovarian putative stem cells (poPSCs), although not pluripotent, are characterized by great plasticity. Therefore, this study aimed to investigate whether poPSCs have the potential to differentiate into cells of endothelial lineage. poPSCs were immunomagnetically isolated from postnatal pig ovaries based on the presence of SSEA-4 protein. Expression of mesenchymal stem cells (MSCs) markers after pre-culture, both at the level of mRNA: ITGB1, THY, and ENG and corresponding protein: CD29, CD90, and CD105 were significantly higher compared to the control ovarian cortex cells. To differentiate poPSCs into ECs, inducing medium containing vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF), epidermal growth factor (EGF), ascorbic acid, and heparin was applied. After 14 days, poPSC differentiation into ECs was confirmed by immunofluorescence staining for vascular endothelial cadherin (VECad) and vascular endothelial growth factor receptor-2 (VEGFR-2). Semi-quantitative WB analysis of these proteins confirmed their high abundance. Additionally, qRT-PCR showed that mRNA expression of corresponding marker genes: CDH5, KDR was significantly higher compared with undifferentiated poPSCs. Finally, EC functional status was confirmed by the migration test that revealed that they were capable of positive chemotaxis, while tube formation assay demonstrated their ability to develop capillary networks. In conclusion, our results provided evidence that poPSCs may constitute the MSC population in the ovary and confirmed that they might be a potential source of ECs for tissue engineering.

scholarly journals Trehalose 6,6′-Dimycolate (Cord Factor) of Mycobacterium tuberculosis Induces Corneal Angiogenesis in Rats

2000 ◽  
Vol 68 (10) ◽  
pp. 5991-5997 ◽  
Author(s):  
Norio Saita ◽  
Nagatoshi Fujiwara ◽  
Ikuya Yano ◽  
Kazuhiko Soejima ◽  
Kazuo Kobayashi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Neutralizing Antibodies ◽  
Early Stage ◽  
Vascular Endothelial ◽  
Cytokine Network ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Cord Factor ◽  
Factor Alpha ◽  
Endothelial Growth Factor

ABSTRACT Neovascularization or angiogenesis is required for the progression of chronic inflammation. The mechanism of inflammatory neovascularization in tuberculosis remains unknown. Trehalose 6,6′-dimycolate (TDM) purified from Mycobacterium tuberculosis was injected into rat corneas. TDM challenge provoked a local granulomatous response in association with neovascularization. Neovascularization was seen within a few days after the challenge, with the extent of neovascularization being dose dependent, although granulomatous lesions developed 14 days after the challenge. Cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-8 (IL-8), IL-1β, and vascular endothelial growth factor (VEGF), were found in lesions at the early stage (within a few days after the challenge) and were detectable until day 21. Neovascularization was inhibited substantially by neutralizing antibodies to VEGF and IL-8 but not IL-1β. Treatment with anti-TNF-α antibodies resulted in partial inhibition. TDM possesses pleiotropic activities, and the cytokine network plays an important role in the process of neovascularization.

scholarly journals Effect of Serum Copper on Circulating Angiogenesis-Related Factors in Women with Preeclampsia

2019 ◽  
Author(s):  
Khalid Najm Nadheer ◽  
Zohreh Zahraei ◽  
Hussein Al-Hakeim
Keyword(s):  
Pregnant Women ◽  
Serum Copper ◽  
Control Group ◽  
Vascular Endothelial ◽  
Related Factors ◽  
Soluble Endoglin ◽  
Iraqi Women ◽  
Endothelial Integrity ◽  
And Control ◽  
Endothelial Growth Factor

Preeclampsia (PE) is characterized by a series of clinical features such as hypertension and proteinuria associated with endothelial dysfunction and the impairment of placenta vascular endothelial integrity. This study aimed to investigate the effect of serum copper (Cu) level on some angiogenesis-related factors including vascular endothelial growth factor-A (VEGF-A), soluble Fms-like tyrosine kinase-1 (sVEGF-R1), soluble endoglin (sEng) and cerruloplasmin (Cp) in Iraqi women with preeclampsia (PE) and control pregnant women. Therefore, 60 women with PE in addition to 30 healthy pregnant women were enrolled in the study. Serum concentration of sEng, VEGF-A, sVEGF-R1, and Cu in PE group significantly increased (p<0.05) in the PE group compared with that in the control group. Increased production of antiangiogenic factors, soluble VEGF-A and sEng contribute to the pathophysiology of PE, indicating the involvement of these parameters in the angiogenic balance in patients with PE. Tests for between-subject effects showed that the circulating angiogenesis factors and Cu were significantly associated with the presence of PE. Serum Cu level was significantly correlated with VEGF- A and VEGF-R1 levels but not with sEng. Multiple regression analysis revealed that only Cp and BP can significantly predict the complications in women with PE. In conclusion, serum Cu has a role in the angiogenesis in women with PE and may be a new drug target in the prevention or treatment of PE.

Ratios between VEGF ligands and receptors in tumor and stroma have impact on the outcome in resectable NSCLC.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22147-e22147 ◽  
Author(s):  
Eloisa Jantus-Lewintre ◽  
Marta Usó ◽  
Elena Sanmartin ◽  
Sandra Gallach ◽  
Rafael Sirera ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Early Stage ◽  
Tumor Stroma ◽  
Wilcoxon Test ◽  
Vascular Endothelial ◽  
Tissue Samples ◽  
Early Stage Nsclc ◽  
Vegf Family Members ◽  
Nsclc Patients ◽  
Endothelial Growth Factor

e22147 Background: In tumor angiogenesis there is a complex interplay between endothelial, stromal and tumor cells. Some key regulators of this process are the members of the vascular endothelial growth factor (VEGF) family of ligands and receptors and the neuropilins (NRP). This study analyzes the correlations between the expression of these angiogenic factors in tumor cells and tumor stroma, and their prognostic role in tissue samples from resected non-small cell lung cancer (NSCLC) patients. Methods: Representative tumor and stroma areas from FFPE tissue samples of 125 early-stage NSCLC patients were carefully micro-dissected. RNA isolated from the samples was retrotranscripted and preamplified. RTqPCR was performed using hydrolysis probes (TaqMan, Applied Biosystems) and relative quantification was calculated using GAPDH and CDKN1B as endogenous controls. Results were normalized against a human cDNA (Clontech) as a reference. All statistical analyses were considered significant at p<0.05. Results: Paired Wilcoxon test revealed differences between tumor and stroma gene expression for VEGFB (p<0.0001), VEGFC (p<0.0001), VEGFR-1 (p<0.0001), VEGFR-2 (p=0.020), VEGFR-3 (p< 0.0001), NRP-1 (p=0.001) and NRP-2 (p< 0.0001). Survival analyses showed that those patients with higher levels of the Ratio Stromal-VEGFA/ Tumoral-VEGFR-2 had worse time to progression (TTP) (median 26.23 months vs NR, p=0.013) and overall survival (OS) (median 29.50 months vs NR, p=0.001). Similarly, those patients with higher levels of the Ratio Stromal-VEGFC/Tumoral-VEGFR-3 had worse TTP (median 23.30 vs 70.53 months, p=0.015) and OS (median 37.20 months vs NR, p=0.023). Conclusions: Our results show significant differences in the expression of VEGF family members between tumor and stromal cells. This may indicate the importance of the tumor-stroma interaction when trying to understand the angiogenic process. Furthermore, the combination of the ligands expression in stroma and their receptors in tumor may have a prognostic value in NSCLC patients. Supported by grants PS09-01149 and RD06/0020/1024 from ISCIII.

scholarly journals Vascular Endothelial Growth Factor in Tear Samples of Patients with Systemic Sclerosis

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Anikó Rentka ◽  
Jolán Hársfalvi ◽  
András Berta ◽  
Krisztina Köröskényi ◽  
Zoltán Szekanecz ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Total Protein ◽  
Protein Production ◽  
Average Concentration ◽  
Vascular Endothelial ◽  
Ophthalmological Examination ◽  
Sample Collection ◽  
Total Protein Level ◽  
And Control ◽  
Endothelial Growth Factor

Background. Systemic sclerosis is an autoimmune disease, characterized by widespread small vessel vasculopathy, immune dysregulation with production of autoantibodies, and progressive fibrosis. Changes in levels of proangiogenic cytokines had already been determined largely in serum. Our aim was to assess the levels of VEGF in human tears of patients with SSC.Patients and methods. Forty-three patients (40 female and 3 men, mean (SD) age 61 (48–74) years) with SSc and 27 healthy controls were enrolled in this study. Basal tear sample collection and tear velocity investigations were carried out followed by an ophthalmological examination. Total protein concentrations and VEGF levels were determined in tear samples.Results. The average collected tear fluid volume developed 10.4 μL (1.6–31.2) in patients and 15.63 μL (3.68–34.5) in control subjects. The average total protein level was 6.9 μg/μL (1.8–12.3) in tears of patients and control tears contained an average of 4.132 μg/μL (0.1–14.1) protein. In patients with SSc the average concentration of VEGF was 4.9 pg/μL (3.5–8.1) and 6.15 pg/μL (3.84–12.3) in healthy samples.Conclusions. Total protein production was increased because of the smaller tear volume. Decreased VEGF in tear of SSc patients can be explained also by the decreased tear secretion of patients.

scholarly journals Modulation of Vascular Endothelial Growth Factor and Annexin A2 in Response to 4-(Methylnitrosamino)-1-(3-pyridyl)-1-Butanone -Induced Inflammation via Swimming Training

2018 ◽  
pp. 418-427
Author(s):  
Ali Barzegari ◽  
Shadmehr Mirdar ◽  
Mohammad Ranayi
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Lung Tissue ◽  
Study Groups ◽  
Annexin A2 ◽  
Vascular Endothelial ◽  
Swimming Training ◽  
Significance Level ◽  
And Control ◽  
Endothelial Growth Factor

The nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; nicotine derived nitrosamine ketone) is one of the strongest carcinogens in tobacco which is involved in induction of lung cancer by changing the stimulation of vascular endothelial growth factor (VEGF) and annexin A2 expression. The aim of this study was to investigate the changes in resting levels of annexin A2 and VEGF in lung tissues of rats exposed NNK after 12 weeks of aerobic submaximal swimming training. For this purpose, 46 Wistar rats were randomly divided into five groups consist of training, training + NNK, NNK, saline and control. NNK-induced groups received NNK subcutaneously one day per week at a rate of 12/5 mg per kg body weight and the training groups performed submaximal swimming training for 12 weeks. The levels of VEGF and annexin A2 in lung tissue were measured respectively by ELISA and immunohistochemistry. To analyze the data; ANOVA and Tukey's test were used at a significance level of p<0.05. Findings indicated that 12 weeks submaximal swimming training decreased the levels of VEGF and annexin A2 in lung tissue significantly when compared to NNK group (p<0.001). There was no significant correlation between VEGF and annexin A2 levels in all study groups (p≥0.05). Generally, it could be confirmed that regular submaximal aerobic training plays an important role in inhibition of the effects of lung inflammation induced by NNK via decreased levels of VEGF and annexin A2.

scholarly journals Genetic polymorphisms of Vascular Endothelial Growth Factor (VEGF) associated with endometriosis in Nigerian women

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Ochuwa Adiketu Babah ◽  
Oyesola Oyewole Ojewunmi ◽  
Akinniyi Adediran Osuntoki ◽  
Melissa A. Simon ◽  
Bosede Bukola Afolabi
Keyword(s):  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Nucleotide Polymorphisms ◽  
Nigerian Women ◽  
Pcr Rflp ◽  
Hardy Weinberg Equilibrium ◽  
Elisa Technique ◽  
Genomic Dnas ◽  
And Control ◽  
Endothelial Growth Factor

Abstract Objective To determine if genetic polymorphism of VEGF is associated with the development of endometriosis in Nigerian women. Study design Case control study of 100 women (50 healthy controls and 50 with endometriosis). Serum VEGF concentration of participants were determined using enzyme-linked immunosorbent assay (ELISA) technique. Genomic DNAs were isolated from peripheral blood samples and quantified by nanodrop spectrophotometer one. Single nucleotide polymorphisms genotyping was carried out by polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP). Results Mean age of participants was 32.96 ± 6.91 years for control and 32.04 ± 7.56 years for cases. VEGF levels in case and control groups were not statistically different (82.68 pg/ml [69.11–121.11 pg/ml] vs. 82.81 pg/ml [72.90–113.82 pg/ml] respectively; p = 0.967). All four genotypes examined were in Hardy–Weinberg equilibrium. Minor allele frequency of − 460T > C, − 1154G > A, + 936C > T and + 2578C > A were 24%, 8%, 6% and 10% in the control and 19%, 9%, 5% and 14% in endometriosis patients. However, allele and genotype distributions of − 460T > C, − 1154G > A, + 936C > T and + 2578C > A VEGF polymorphisms in endometriosis patients and control were not significantly different (p > 0.05). Conclusion Our preliminary findings revealed no association between endometriosis and − 460T > C, − 1154G > A, + 936C > T and + 2578C > A of VEGF genes among Nigerian women.

scholarly journals The Role of the VEGF Family in Coronary Heart Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Yan Zhou ◽  
Xueping Zhu ◽  
Hanming Cui ◽  
Jingjing Shi ◽  
Guozhen Yuan ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Early Stage ◽  
Lymphatic Vessels ◽  
Review Article ◽  
Target Cells ◽  
Vascular Endothelial ◽  
Cardiac Recovery ◽  
Endothelial Growth Factor

The vascular endothelial growth factor (VEGF) family, the regulator of blood and lymphatic vessels, is mostly investigated in the tumor and ophthalmic field. However, the functions it enjoys can also interfere with the development of atherosclerosis (AS) and further diseases like coronary heart disease (CHD). The source, regulating mechanisms including upregulation and downregulation, target cells/tissues, and known functions about VEGF-A, VEGF-B, VEGF-C, and VEGF-D are covered in the review. VEGF-A can regulate angiogenesis, vascular permeability, and inflammation by binding with VEGFR-1 and VEGFR-2. VEGF-B can regulate angiogenesis, redox, and apoptosis by binding with VEGFR-1. VEGF-C can regulate inflammation, lymphangiogenesis, angiogenesis, apoptosis, and fibrogenesis by binding with VEGFR-2 and VEGFR-3. VEGF-D can regulate lymphangiogenesis, angiogenesis, fibrogenesis, and apoptosis by binding with VEGFR-2 and VEGFR-3. These functions present great potential of applying the VEGF family for treating CHD. For instance, angiogenesis can compensate for hypoxia and ischemia by growing novel blood vessels. Lymphangiogenesis can degrade inflammation by providing exits for accumulated inflammatory cytokines. Anti-apoptosis can protect myocardium from impairment after myocardial infarction (MI). Fibrogenesis can promote myocardial fibrosis after MI to benefit cardiac recovery. In addition, all these factors have been confirmed to keep a link with lipid metabolism, the research about which is still in the early stage and exact mechanisms are relatively obscure. Because few reviews have been published about the summarized role of the VEGF family for treating CHD, the aim of this review article is to present an overview of the available evidence supporting it and give hints for further research.

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