Show simple item record

dc.contributor.authorToivanen Pyry I
dc.contributor.authorNieminen Tiina
dc.contributor.authorLaakkonen Johanna P
dc.contributor.authorHeikura Tommi
dc.contributor.authorKaikkonen Minna U
dc.contributor.authorYlä-Herttuala Seppo
dc.date.accessioned2017-11-30T14:03:58Z
dc.date.available2017-11-30T14:03:58Z
dc.date.issued2017
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/5043
dc.description.abstractVascular 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.en
dc.language.isoENen
dc.publisherSpringer Natureen
dc.relation.ispartofseriesScientific Reportsen
dc.relation.urihttp://dx.doi.org/10.1038/s41598-017-05876-yen
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/en
dc.subjectBiochemistryen
dc.subjectMolecular biologyen
dc.subjectMolecular medicineen
dc.subjectStructural biologyen
dc.titleSnake venom VEGF Vammin induces a highly efficient angiogenic response in skeletal muscle via VEGFR-2/NRP specific signalingen
dc.description.versionpublished versionen
dc.contributor.departmentA.I. Virtanen -instituuttien
dc.contributor.departmentA.I. Virtanen -instituutti / Bioteknologia ja molekulaarinen lääketiedeen
uef.solecris.id48860463en
dc.type.publicationinfo:eu-repo/semantics/articleen
dc.rights.accessrights© Authorsen
dc.relation.doi10.1038/s41598-017-05876-yen
dc.description.reviewstatuspeerRevieweden
dc.relation.articlenumber5525
dc.relation.issn2045-2322en
dc.relation.volume7en
dc.rights.accesslevelopenAccessen
dc.type.okmA1en
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
uef.solecris.openaccessOpen access -julkaisukanavassa ilmestynyt julkaisu


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record