ArticleThe Journal of biological chemistry2015
Synergistic Binding of Vascular Endothelial Growth Factor-A and Its Receptors to Heparin Selectively Modulates Complex Affinity.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 69 citations in OpenAlex.
- Mechanisms of VEGFR2 activation by VEGF, neuropilin, and heparin.Science advances · 2026Article
- Endothelial Surface Glycocalyx in Vascular Functions and Diseases.Advances in experimental medicine and biology · 2026Review
- Therapeutic Reprogramming of Glioblastoma Phenotypic States Using Multifunctional Heparin Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Glycosaminoglycans, Instructive Biomolecules That Regulate Cellular Activity and Synaptic Neuronal Control of Specific Tissue Functional Properties.International journal of molecular sciences · 2025Review
- Alteration of Neuropilin-1 and Heparan Sulfate Interaction Impairs Murine B16 Tumor Growth.ACS chemical biology · 2024Article
- Discovery and Characteristics of a Novel Antitumor Cyclopeptide Derived from Shark.Bioengineering (Basel, Switzerland) · 2023Article
- Effects of systemic anticoagulation in a murine model of compensatory lung growth.Pediatric research · 2023Article
- Alterations in heparan sulfate proteoglycan synthesis and sulfation and the impact on vascular endothelial function.Matrix biology plus · 2022Review
- The Future of the COVID-19 Pandemic: How Good (or Bad) Can the SARS-CoV2 Spike Protein Get?Cells · 2022Review
- A widespread viral entry mechanism: The C-end Rule motif-neuropilin receptor interaction.Proceedings of the National Academy of Sciences of the United States of America · 2021Review
- Peptide Inhibitors of Vascular Endothelial Growth Factor A: Current Situation and Perspectives.Pharmaceutics · 2021Review
- Recent Progress on Cellulose-Based Ionic Compounds for Biomaterials.Advanced materials (Deerfield Beach, Fla.) · 2021Review
- Neuropilin-1: A feasible link between liver pathologies and COVID-19.World journal of gastroenterology · 2021Review
- Investigation of the mechanisms of VEGF-mediated compensatory lung growth: the role of the VEGF heparin-binding domain.Scientific reports · 2021Article
- Sulfated glycans engage the Ang-Tie pathway to regulate vascular development.Nature chemical biology · 2021Article
- Effect of a Neuropilin-1-Derived Virus Receptor Trap on Enterovirus A71 InfectionAntimicrobial agents and chemotherapy · 2020Article
- Article
- Heparinoid Complex-Based Heparin-Binding Cytokines and Cell Delivery Carriers.Molecules (Basel, Switzerland) · 2019Review
- Dual Action of Sulfated Hyaluronan on Angiogenic Processes in Relation to Vascular Endothelial Growth Factor-A.Scientific reports · 2019Article
- Heparin potentiates Avastin-mediated inhibition of VEGF binding to fibronectin and rescues Avastin activity at acidic pH.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Angiogenesis is a highly regulated process orchestrated by the VEGF system. Heparin/heparan sulfate proteoglycans and neuropilin-1 (NRP-1) have been identified as co-receptors, yet the mechanisms of action have not been fully defined. In the present study, we characterized molecular interactions between receptors and co-receptors, using surface plasmon resonance and in vitro binding assays. Additionally, we demonstrate that these binding events are relevant to VEGF activity within endothelial cells. We defined interactions and structural requirements for heparin/HS interactions with VEGF receptor (VEGFR)-1, NRP-1, and VEGF165 in complex with VEGFR-2 and NRP-1. We demonstrate that these structural requirements are distinct for each interaction. We further show that VEGF165, VEGFR-2, and monomeric NRP-1 bind weakly to heparin alone yet show synergistic binding to heparin when presented together in various combinations. This synergistic binding appears to translate to alterations in VEGF signaling in endothelial cells. We found that soluble NRP-1 increases VEGF binding and activation of VEGFR-2 and ERK1/2 in endothelial cells and that these effects require sulfated HS. These data suggest that the presence of HS/heparin and NRP-1 may dictate the specific receptor type activated by VEGF and ultimately determine the biological output of the system. The ability of co-receptors to fine-tune VEGF responsiveness suggests the possibility that VEGF-mediated angiogenesis can be selectively stimulated or inhibited by targeting HS/heparin and NRP-1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.