scholarly journals Toll-Like Receptor Signalling Pathways Regulate Hypoxic Stress Induced Fibroblast Growth Factor but Not Vascular Endothelial Growth Factor-A in Human Microvascular Endothelial Cells

2021 ◽  
Vol 1 (1) ◽  
pp. 25-38
Author(s):  
Rukhsar Akhtar ◽  
Husain Tahir ◽  
Elizabeth Stewart ◽  
Ruoxin Wei ◽  
Imran Mohammed ◽  
...  
Keyword(s):  
Growth Factor ◽  
Microvascular Endothelial Cells ◽  
Signalling Pathways ◽  
Retinal Diseases ◽  
Vascular Endothelial ◽  
Hypoxic Stress ◽  
Fibroblast Growth ◽  
Toll Like Receptor ◽  
Endothelial Growth Factor ◽  
Tlr Signalling

Retinal diseases are the leading causes of irreversible blindness worldwide. The role of toll-like receptor (TLR) signalling mechanisms (MyD88 and TRIF) in the production of pro-angiogenic growth factors from human microvascular endothelial cells (HMEC-1) under hypoxic stress remains unexplored. HMEC-1 was incubated under normoxic (5% CO2 at 37 °C) and hypoxic (1% O2, 5% CO2, and 94% N2; at 37 °C) conditions for 2, 6, 24, and 48 h, respectively. For TLR pathway analysis, HMEC-1 was pre-treated with pharmacological inhibitors (Pepinh-MyD88 and Pepinh-TRIF) and subjected to normoxia and hypoxia conditions. Gene and protein expressions of vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor (FGF-2), hypoxia inducible factor 1-alpha (HIF1-α) were performed using quantitative polymerase chain reaction (qPCR), ELISA, and Western blot methodologies. Levels of TLR3 and TLR4 were analysed by flow cytometry. Under hypoxia, levels of VEGF-A and FGF-2 were elevated in a time-dependent fashion. Inhibition of MyD88 and TRIF signalling pathways decreased FGF-2 levels but failed to modulate the secretion of VEGF-A from HMEC-1. Blocking a known regulator, endothelin receptor (ETR), also had no effect on VEGF-A secretion from HMEC-1. Overall, this study provides the proof-of-concept to target TLR signalling pathways for the management of blinding retinal diseases.

Synergistic Induction of t-PA by Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor and Localization of t-PA to Weibel-Palade Bodies in Bovine Microvascular Endothelial Cells

2001 ◽  
Vol 86 (08) ◽  
pp. 702-709 ◽  
Author(s):  
Corinne Rosnoblet ◽  
Corinne Di Sanza ◽  
Egbert Kruithof ◽  
Michael Pepper
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Microvascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Fibroblast Growth ◽  
Endothelial Growth Factor

SummaryEndothelial cell migration is stimulated by members of the vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) families, and is dependent on extracellular proteolytic activity provided by enzymes of the plasminogen activator (PA) system. Here we report that in bovine microvascular endothelial cells (BME cells), bFGF principally increased urokinase-type PA (u-PA) while tissue-type PA (t-PA) was increased mainly by VEGF. In bovine aortic endothelial cells (BAE cells), bFGF increased u-PA, whereas VEGF had no effect. Co-added bFGF and VEGF increased t-PA mRNA levels and enzyme activity in both cell types in a synergistic manner. Tissue-type plasminogen activator (t-PA) immunoreactivity colocalized with von Willebrand factor, a marker for Weibel-Palade bodies. Co-added bFGF and VEGF increased the number of t-PA-positive cells as well as the number of t-PA-positive granules per cell. Localization of t-PA in regulated storage granules endows endothelial cells with the potential to rapidly increase proteolytic activity in the pericellular environment.

Effect of Acellular Bovine Pericardium and Urinary Bladder Submucosa Matrixes in Reconstruction of Ventro-Lateral Hernias in Bucks; Molecular Evaluation

2019 ◽  
Vol 43 (1) ◽  
pp. 67-74
Author(s):  
Areeg K. M. Al-ebadi
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Treatment Group ◽  
Urinary Bladder ◽  
Bovine Pericardium ◽  
Vascular Endothelial ◽  
Fibroblast Growth ◽  
Urinary Bladder Matrix ◽  
Endothelial Growth Factor ◽  
Molecular Evaluation

The present study aimed to estimate the efficiency of both a cellular bovine pericardium and bovine urinary bladder matrix sheets in the reconstruction of large ventro-lateral hernias in Iraqi bucks by using of molecular evaluation depending on real time-polymerase chain reaction technique to investigate the level of basic-fibroblast growth factor  and vascular endothelial growth factor  genes during the healing process and reconstruction of the abdominal defects. Under sedation and local anesthesia, (6cm X 8cm size) of ventro-lateral hernias were induced in 24 of Iraqi bucks. The animals were divided randomly into two main equal groups. In bovine pericardium-treatment group, the hernias were treated with onlay implantation of bovine pericardium. While, the hernias in UBM-treatment group were treated with onlay implantation of urinary bladder matrix, 30 days post-inducing of hernias. The molecular evaluation along the period of following-up recorded a significant up-regulation of the level of basic-fibroblast growth factor gene specific for presence of fibroblasts, myofibroblasts and collagen deposition in urinary bladder matrix -treatment group in comparison to bovine pericardium -treatment group with significant difference even at the end of the study. While, a significant up regulation of the levels of angiogenesis classic gene vascular endothelial growth factor  were recorded in the bucks of bovine pericardium -treatment group compared to urinary bladder matrix -treatment group. In conclusion; molecular detection of the level of growth factors in target tissue can be used as an important criterion.

scholarly journals Microvascularization and Expression of Fibroblast Growth Factor and Vascular Endothelial Growth Factor and Their Receptors in the Mare Oviduct

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1099
Author(s):  
Pedro Pinto-Bravo ◽  
Maria Rosa Rebordão ◽  
Ana Amaral ◽  
Carina Fernandes ◽  
António Galvão ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Microvascular Density ◽  
Angiogenic Factors ◽  
Protein Abundance ◽  
Vascular Endothelial ◽  
Fibroblast Growth ◽  
Vascular Area ◽  
Endothelial Growth Factor

The oviduct presents the ideal conditions for fertilization and early embryonic development. In this study, (i) vascularization pattern; (ii) microvascular density; (iii) transcripts of angiogenic factors (FGF1, FGF2, VEGF) and their receptors—FGFR1, FGFR2, KDR, respectively, and (iv) the relative protein abundance of those receptors were assessed in cyclic mares’ oviducts. The oviductal artery, arterioles and their ramifications, viewed by means of vascular injection-corrosion, differed in the infundibulum, ampulla and isthmus. The isthmus, immunostained with CD31, presented the largest vascular area and the highest number of vascular structures in the follicular phase. Transcripts (qPCR) and relative protein abundance (Western blot) of angiogenic factors fibroblast growth factor 1 (FGF1) and 2 (FGF2) and vascular endothelial growth factor (VEGF), and their respective receptors (FGFR1, FGFR2, VEGFR2 = KDR), were present in all oviduct portions throughout the estrous cycle. Upregulation of the transcripts of angiogenic receptors FGF1 and FGFR1 in the ampulla and isthmus and of FGF2 and KDR in the isthmus were noted. Furthermore, in the isthmus, the relative protein abundance of FGFR1 and KDR was the highest. This study shows that the equine oviduct presents differences in microvascular density in its three portions. The angiogenic factors VEGF, FGF1, FGF2 and their respective receptors are expressed in all studied regions of the mare oviduct, in agreement with microvascular patterns.

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