The Role of Heparan Sulfate and Neuropilin 2 in VEGFA Signaling in Human Endothelial Tip Cells and Non-Tip Cells during Angiogenesis In Vitro
| Autor: | Cornelis J.F. Van Noorden, Marchien G. Dallinga, Ingeborg Klaassen, Alinda W. M. Schimmel, Geesje M. Dallinga-Thie, Reinier O. Schlingemann, Yasmin Habani |
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| Přispěvatelé: | ACS - Atherosclerosis & ischemic syndromes, ANS - Cellular & Molecular Mechanisms, ANS - Systems & Network Neuroscience, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Experimental Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, ACS - Diabetes & metabolism, Medical Biology, Ophthalmology, ACS - Microcirculation |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Vascular Endothelial Growth Factor A
VEGFA Very low-density lipoprotein endocrine system Angiogenesis QH301-705.5 Neovascularization Physiologic Apoptosis SULF2 Lipoproteins VLDL Article Extracellular matrix chemistry.chemical_compound angiogenesis Human Umbilical Vein Endothelial Cells Humans NRP2 Biology (General) Sprouting angiogenesis Gene knockdown Chemistry General Medicine Heparan sulfate tip cells Vascular Endothelial Growth Factor Receptor-2 endothelial cells Cell biology Neuropilin-2 Endothelial stem cell Vascular endothelial growth factor A cardiovascular system HSPG Heparitin Sulfate Sulfatases Signal Transduction |
| Zdroj: | Cells, Vol 10, Iss 926, p 926 (2021) Cells Volume 10 Issue 4 Cells, 10(4):926. MDPI Multidisciplinary Digital Publishing Institute |
| ISSN: | 2073-4409 |
| Popis: | During angiogenesis, vascular endothelial growth factor A (VEGFA) regulates endothelial cell (EC) survival, tip cell formation, and stalk cell proliferation via VEGF receptor 2 (VEGFR2). VEGFR2 can interact with VEGFR2 co-receptors such as heparan sulfate proteoglycans (HSPGs) and neuropilin 2 (NRP2), but the exact roles of these co-receptors, or of sulfatase 2 (SULF2), an enzyme that removes sulfate groups from HSPGs and inhibits HSPG-mediated uptake of very low density lipoprotein (VLDL), in angiogenesis and tip cell biology are unknown. In the present study, we investigated whether the modulation of binding of VEGFA to VEGFR2 by knockdown of SULF2 or NRP2 affects sprouting angiogenesis, tip cell formation, proliferation of non-tip cells, and EC survival, or uptake of VLDL. To this end, we employed VEGFA splice variant 121, which lacks an HSPG binding domain, and VEGFA splice variant 165, which does have this domain, in in vitro models of angiogenic tip cells and vascular sprouting. We conclude that VEGFA165 and VEGFA121 have similar inducing effects on tip cells and sprouting in vitro, and that the binding of VEGFA165 to HSPGs in the extracellular matrix does not seem to play a role, as knockdown of SULF2 did not alter these effects. Co-binding of NRP2 appears to regulate VEGFA–VEGFR2-induced sprout initiation, but not tip cell formation. Finally, as the addition of VLDL increased sprout formation but not tip cell formation, and as VLDL uptake was limited to non-tip cells, our findings suggest that VLDL plays a role in sprout formation by providing biomass for stalk cell proliferation. |
| Databáze: | OpenAIRE |
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