We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Dual Action of Sulfated Hyaluronan on Angiogenic Processes in Relation to Vascular Endothelial Growth Factor-A.
- Authors
Koehler, Linda; Ruiz-Gómez, Gloria; Balamurugan, Kanagasabai; Rother, Sandra; Freyse, Joanna; Möller, Stephanie; Schnabelrauch, Matthias; Köhling, Sebastian; Djordjevic, Snezana; Scharnweber, Dieter; Rademann, Jörg; Pisabarro, M. Teresa; Hintze, Vera
- Abstract
Pathological healing characterized by abnormal angiogenesis presents a serious burden to patients' quality of life requiring innovative treatment strategies. Glycosaminoglycans (GAG) are important regulators of angiogenic processes. This experimental and computational study revealed how sulfated GAG derivatives (sGAG) influence the interplay of vascular endothelial growth factor (VEGF)165 and its heparin-binding domain (HBD) with the signaling receptor VEGFR-2 up to atomic detail. There was profound evidence for a HBD-GAG-HBD stacking configuration. Here, the sGAG act as a "molecular glue" leading to recognition modes in which sGAG interact with two VEGF165-HBDs. A 3D angiogenesis model demonstrated the dual regulatory role of high-sulfated derivatives on the biological activity of endothelial cells. While GAG alone promote sprouting, they downregulate VEGF165-mediated signaling and, thereby, elicit VEGF165-independent and -dependent effects. These findings provide novel insights into the modulatory potential of sGAG derivatives on angiogenic processes and point towards their prospective application in treating abnormal angiogenesis.
- Subjects
HYALURONIC acid; VASCULAR endothelial growth factors; QUALITY of life; GLYCOSAMINOGLYCANS; ENDOTHELIAL cells
- Publication
Scientific Reports, 2019, Vol 9, Issue 1, pN.PAG
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-019-54211-0