Snake venom VEGF Vammin induces a highly efficient angiogenic response in skeletal muscle via VEGFR-2/NRP specific signaling
| Autor: | Minna U. Kaikkonen, Seppo Ylä-Herttuala, Tommi Heikura, Johanna P. Laakkonen, Pyry I. Toivanen, Tiina Nieminen |
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| Přispěvatelé: | A.I. Virtanen -instituutti, A.I. Virtanen -instituutti / Bioteknologia ja molekulaarinen lääketiede |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Vascular Endothelial Growth Factor A medicine.medical_specialty Angiogenesis Molecular biology Science Neovascularization Physiologic Nerve Tissue Proteins Viper Venoms Biology Biochemistry Article Neovascularization 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Human Umbilical Vein Endothelial Cells Animals Humans Therapeutic angiogenesis Amino Acid Sequence Muscle Skeletal Calcium signaling Cell Proliferation Regulation of gene expression Sprouting angiogenesis Multidisciplinary Molecular medicine Snakes Vascular Endothelial Growth Factor Receptor-2 Recombinant Proteins Cell biology Protein Structure Tertiary 030104 developmental biology Endocrinology Nuclear receptor Medicine Rabbits Signal transduction medicine.symptom Mitogen-Activated Protein Kinases Structural biology Sequence Alignment 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
| Popis: | Vascular Endothelial Growth Factors (VEGFs) are promising molecules for the treatment of ischemic diseases by pro-angiogenic therapy. Snake venom VEGFs are a novel subgroup with unique receptor binding profiles and as such are potential new therapeutic agents. We determined the ligand-receptor interactions, gene regulation and angiogenic properties of Vipera ammodytes venom VEGF, Vammin, and compared it to the canonical angiogenic factor VEGF-A to evaluate the use of Vammin for therapeutic angiogenesis. Vammin efficiently induced VEGFR-2 mediated proliferation and expression of genes associated with proliferation, migration and angiogenesis. VEGF-A165 and especially VEGF-A109 induced less pronounced effects. Vammin regulates a number of signaling pathways by inducing the expression of NR4A family nuclear receptors and regulators of calcium signaling and MAP kinase pathways. Interestingly, MARC1, which encodes an enzyme discovered to catalyze reduction of nitrate to NO, was identified as a novel VEGFR-2 regulated gene. In rabbit skeletal muscle adenoviral delivery of Vammin induced prominent angiogenic responses. Both the vector dose and the co-receptor binding of the ligand were critical parameters controlling the type of angiogenic response from sprouting angiogenesis to vessel enlargement. Vammin induced VEGFR-2/NRP-1 mediated signaling more effectively than VEGF-A, consequently it is a promising candidate for development of pro-angiogenic therapies. published version peerReviewed |
| Databáze: | OpenAIRE |
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