scholarly journals Binding affinities of vascular endothelial growth factor (VEGF) for heparin-derived oligosaccharides

2011 ◽  
Vol 32 (1) ◽  
pp. 71-81 ◽  
Author(s):  
Wenjing Zhao ◽  
Scott A. McCallum ◽  
Zhongping Xiao ◽  
Fuming Zhang ◽  
Robert J. Linhardt
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Binding Affinity ◽  
Structural Features ◽  
Minimum Size ◽  
Vascular Endothelial ◽  
Binding Affinities ◽  
Angiogenic Growth Factors ◽  
Protein Ligands ◽  
Endothelial Growth Factor

Heparin and HS (heparan sulfate) exert their wide range of biological activities by interacting with extracellular protein ligands. Among these important protein ligands are various angiogenic growth factors and cytokines. HS binding to VEGF (vascular endothelial growth factor) regulates multiple aspects of vascular development and function through its specific interaction with HS. Many studies have focused on HS-derived or HS-mimicking structures for the characterization of VEGF165 interaction with HS. Using a heparinase 1-prepared small library of heparin-derived oligosaccharides ranging from hexasaccharide to octadecasaccharide, we systematically investigated the heparin-specific structural features required for VEGF binding. We report the apparent affinities for the association between the heparin-derived oligosaccharides with both VEGF165 and VEGF55, a peptide construct encompassing exclusively the heparin-binding domain of VEGF165. An octasaccharide was the minimum size of oligosaccharide within the library to efficiently bind to both forms of VEGF and a tetradecasaccharide displayed an effective binding affinity to VEGF165 comparable to unfractionated heparin. The range of relative apparent binding affinities among VEGF and the panel of heparin-derived oligosaccharides demonstrate that the VEGF binding affinity likely depends on the specific structural features of these oligosaccharides, including their degree of sulfation, sugar-ring stereochemistry and conformation. Notably, the unique 3-O-sulfo group found within the specific antithrombin binding site of heparin is not required for VEGF165 binding. These findings afford new insight into the inherent kinetics and affinities for VEGF association with heparin and heparin-derived oligosaccharides with key residue-specific modifications and may potentially benefit the future design of oligosaccharide-based anti-angiogenesis drugs.

scholarly journals Large adipose tissue generation in a mussel-inspired bioreactor of elastic–mimetic cryogel and platelets

2018 ◽  
Vol 9 ◽  
pp. 204173141880863 ◽  
Author(s):  
Qiang Chang ◽  
Junrong Cai ◽  
Ying Wang ◽  
Ruijia Yang ◽  
Malcolm Xing ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Adipose Tissue ◽  
Growth Factor ◽  
Cellular Proliferation ◽  
Platelet Derived Growth Factor ◽  
Control Group ◽  
Vascular Endothelial ◽  
Angiogenic Growth Factors ◽  
Congenital Deformities ◽  
Endothelial Growth Factor

Soft tissue generation, especially in large tissue, is a major challenge in reconstructive surgery to treat congenital deformities, posttraumatic repair, and cancer rehabilitation. The concern is along with the donor site morbidity, donor tissue shortage, and flap necrosis. Here, we report a dissection-free adipose tissue chamber–based novel guided adipose tissue regeneration strategy in a bioreactor of elastic gelatin cryogel and polydopamine-assisted platelet immobilization intended to improve angiogenesis and generate large adipose tissue in situ. In order to have matched tissue mechanics, we used 5% gelatin cryogel as growth substrate of bioreactor. Platelets from the platelet-rich plasma were then immobilized onto the gelatin cryogel with the aid of polydopamine to form a biomimetic bioreactor (polydopamine/gelatin cryogel/platelet). Platelets on the substrate led to a sustained high release in both platelet-derived growth factor and vascular endothelial growth factor compared with non-polydopamine-assisted group. The formed bioreactor was then transferred to a tissue engineering chamber and then inserted above inguinal fat pad of rats without flap dissection. This integrate strategy significantly boomed the vessel density, stimulated cellular proliferation, and upregulated macrophage infiltration. There was a noticeable rise in the expression of dual-angiogenic growth factors (platelet-derived growth factor and vascular endothelial growth factor) in chamber fluid; host cell migration and host fibrous protein secretion coordinated with gelatin cryogel degradation. The regenerated adipose tissue volume gained threefold larger than control group (p < 0.05) with less fibrosis tissue. These results indicate that a big well-vascularized three-dimensional mature adipose tissue can be regenerated using elastic gel, polydopamine, platelets, and small fat tissue.

Post-cyclosporine-mediated hypertension and nephropathy: amelioration by vascular endothelial growth factor

2001 ◽  
Vol 280 (4) ◽  
pp. F727-F736 ◽  
Author(s):  
Duk-Hee Kang ◽  
Yoon-Goo Kim ◽  
Takeshi F. Andoh ◽  
Katherine L. Gordon ◽  
Shin-Ichi Suga ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
High Salt ◽  
Vascular Endothelial ◽  
Tubulointerstitial Injury ◽  
Angiogenic Growth Factors ◽  
High Salt Diet ◽  
Salt Diet ◽  
Salt Sensitive Hypertension ◽  
Endothelial Growth Factor

Recent studies have demonstrated a role for microvascular and tubulointerstitial injury in some models of salt-sensitive hypertension. We utilized a model of post-cyclosporin A (CsA) nephropathy and hypertension to test the hypothesis that treatment with an angiogenic factor aimed at ameliorating the microvascular and renal injury would prevent the development of hypertension. CsA was administered with a low-salt diet for 45 days, resulting in a renal lesion characterized by afferent arteriolopathy, focal peritubular capillary loss, and tubulointerstitial fibrosis. Rats were then placed on a high-salt diet and randomized to receive either vascular endothelial growth factor (VEGF121) or vehicle for 14 days. Placement of rats with established CsA nephropathy on a high-salt diet results in the rapid development of salt-sensitive hypertension. VEGF121 treatment resulted in lower blood pressure, and this persisted on discontinuing the VEGF. VEGF121 treatment was also associated with a decrease in osteopontin expression, macrophage infiltration, and collagen III deposition and markedly stimulated resolution of the arteriolopathy (20.9 ± 7.8 vs. 36.9 ± 6.1%, VEGF vs. vehicle, P < 0.05). In conclusion, CsA-associated renal microvascular and tubulointerstitial injury results in the development of salt-sensitive hypertension. Treatment of animals with established CsA nephropathy with VEGF reduces the hypertensive response and accelerates histological recovery. The vascular protective effect of VEGF may be due to the improvement of arteriolopathy. Angiogenic growth factors may represent a novel strategy for treating CsA-associated hypertension and renal disease.

Vascular Endothelial Growth Factor-A (VEGF-A) Single Nucleotide Polymorphisms and Endometriosis: Still a Controversial Issue

2009 ◽  
Vol 1 (2) ◽  
pp. 94-101 ◽  
Author(s):  
Guido Bocci ◽  
Alessandro Fasciami ◽  
Paola Orlandi ◽  
Antonello di Paolo ◽  
Mario Del Tacca ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Single Nucleotide Polymorphisms ◽  
Published Data ◽  
Vascular Endothelial ◽  
Nucleotide Polymorphisms ◽  
Angiogenic Growth Factors ◽  
Single Nucleotide ◽  
Number Of Patients ◽  
Endothelial Growth Factor

Endometriosis is a chronic, multifactorial, polygenic gynecological disease. Endometrium has a high angiogenic potential and endometriotic lesions involve large areas with a rich blood supply. Angiogenesis is controlled by numerous inducers, including the vascular endothelial growth factor (VEGF) family. Endometrium undergoes cyclical growth and regression during the menstrual cycle, which depends on ovarian steroid levels and is a rich source of angiogenic growth factors, including VEGF-A. The VEGF-A gene is located on chromosome 6p21.3 and it is highly polymorphic with more than 20 different variants. This article critically reviews the published data concerning the relationships between some of the VEGF-A single nucleotide polymorphisms and the risk, pathogenesis and stage of endometriosis. Contrasting results have been published in the literature - probably due to the different ethnic background and the number of patients enrolled in clinical trials. However, the increasing interest in the use of antiangiogenic drugs (eg anti-VEGF-A drugs) in the therapy of endometriosis may suggest carrying out further genetic and pharmacogenetic studies of this disease because the stratification of patients at risk of endometriosis can lead to early diagnosis and optimal treatment choice.

scholarly journals Serum Levels of Asymmetric Dimethylarginine, Vascular Endothelial Growth Factor, and Nitric Oxide Metabolite Levels in Preeclampsia Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Marjan Noorbakhsh ◽  
Maryam Kianpour ◽  
Mehdi Nematbakhsh
Keyword(s):  
Nitric Oxide ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Pregnant Women ◽  
Asymmetric Dimethylarginine ◽  
Serum Levels ◽  
Hypertensive Disorder ◽  
Vascular Endothelial ◽  
Angiogenic Growth Factors ◽  
Endothelial Growth Factor

Background. Hypertensive disorder generally complicates 5–10 percent of all pregnancies. Angiogenic growth factors may be helpful for the diagnosis and prediction of preeclampsia. Therefore, in this study we attempted to determine the serum levels of asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), and nitric oxide (NO) metabolite (nitrite) in preeclampsia patients and compared the levels with those obtained from normal pregnant women. Methods. Ninety pregnant women (19–33 years old) in two groups of preeclampsia and normal were considered during 2012. The levels of ADMA, VEGF, and nitrite were measured in maternal serum samples using ELISA kits. Results. Significant increase of VEGF and nitrite levels was observed in preeclampsia patients when compared with other groups (P<0.05). The serum level of ADMA demonstrated a similar increased trend in preeclampsia patients; however, the increase was not statistically significant (P=0.08). Conclusion. The findings reveal that the elevation of serum levels of VEGF and nitrite and possibly ADMA may be involved in the pathogenesis of preeclampsia.

scholarly journals Characterization of Neuropilin-1 Structural Features That Confer Binding to Semaphorin 3A and Vascular Endothelial Growth Factor 165

2002 ◽  
Vol 277 (20) ◽  
pp. 18069-18076 ◽  
Author(s):  
Chenghua Gu ◽  
Brian J. Limberg ◽  
G. Brian Whitaker ◽  
Ben Perman ◽  
Daniel J. Leahy ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Structural Features ◽  
Vascular Endothelial ◽  
Semaphorin 3A ◽  
Neuropilin 1 ◽  
Endothelial Growth Factor

scholarly journals Direct binding of hepatocyte growth factor and vascular endothelial growth factor to CD44v6

2015 ◽  
Vol 35 (4) ◽  
Author(s):  
Yvonne Volz ◽  
David Koschut ◽  
Alexandra Matzke-Ogi ◽  
Marina S. Dietz ◽  
Christos Karathanasis ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Binding Affinities ◽  
Direct Binding ◽  
Endothelial Growth Factor ◽  
Hepatocyte Growth

CD44v6 is a co-receptor for the receptor tyrosine kinases Met and VEGFR-2 (vascular endothelial growth factor receptor 2). The binding of these RTKs (receptor tyrosine kinases) to their ligands on cells requires CD44v6. Pull-downs assays show direct binding between these entities. Binding affinities were measured by several biophysical methods.

In silico docking studies of Vascular Endothelial Growth Factor-A (VEGFA): Possible Implications in Chronic Myeloid Leukemia (CML) Therapy

2020 ◽  
Vol 17 ◽  
Author(s):  
Samyuktha Lakkireddy ◽  
Archana Jayaraman ◽  
Sangeetha Aula ◽  
Atya Kapley ◽  
Vijay Kumar Kutala ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Chronic Myeloid Leukemia ◽  
Binding Affinity ◽  
In Silico ◽  
Myeloid Leukemia ◽  
Vascular Endothelial ◽  
Ginsenoside Rg3 ◽  
In Silico Docking ◽  
Endothelial Growth Factor

Background: Dysregulated angiogenesis resulting in neovascularization is a critical event in the expansion and progression of Chronic Myeloid Leukemia (CML), a hematopoietic cancer. Vascular Endothelial Growth Factor- A (VEGFA), an important angiogenesis mediator, has been a target for treating cancer. Although several anti-VEGFA drugs are available, they are associated with adverse side effects, promoting the need to identify better drugs that may be less toxic. Objective: Our aim was to investigate whether Tyrosine Kinase Inhibitors (TKIs) could be repurposed for use as VEGFA inhibitors via in silico docking software. We also investigated the potential of phytochemicals as VEGFA inhibitors. Methods: We performed molecular docking using Schrödinger Maestro software suite 2014-3 to determine the most potent phytochemical and TKI VEGFA antagonists. Results: Among the TKIs investigated, Bosutinib had the best binding affinity and may be the most potent TKI against VEGFA. The order of binding affinities for the top ten docked ligands were: Ginsenoside Rg3> Bosutinib> Vitamin D> Paclitaxel> Dasatinib> Saponins> Ponatinib> Squalamine> Imatinib> Nilotinib. We found that Ginsenoside Rg3 had the highest binding affinity (MMGBSA score= -99.4 kcal/mol, glide Gscore = -9.16 kcal/mol) to VEGFA. Conclusion: Our study has shown for the first time the binding poses of these TKIs and phytochemicals to VEGFA, using computational methods. We propose that the use of the top scoring ligands, in isolation or a combination of phytochemicals plus TKI, could serve as potent angiogenesis inhibitors via their binding to and inhibiting VEGFA expression to prevent CML progression. We have also profiled the ligand binding residues which may be explored in designing pharmacophores.

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