title: Functional and pharmacological characterization of a VEGF mimetic peptide on reparative angiogenesis.
abstract: Vascular endothelial growth factor (VEGF) is the main regulator of physiological and pathological angiogenesis. Low molecular weight molecules able to stimulate angiogenesis have interesting medical application for example in regenerative medicine, but at present none has reached the clinic. We reported that a VEGF mimetic helical peptide, QK, designed on the VEGF helix sequence 17-25, is able to bind and activate the VEGF receptors, producing angiogenesis. In this study we evaluate the pharmacological properties of peptide QK with the aim to propose it as a VEGF-mimetic drug to be employed in reparative angiogenesis. We show that the peptide QK is able to recapitulate all the biological activities of VEGF in vivo and on endothelial cells. In experiments evaluating sprouting from aortic ring and vessel formation in an in vivo angiogenesis model, the peptide QK showed biological effects comparable with VEGF. At endothelial level, the peptide up-regulates VEGF receptor expression, activates intracellular pathways depending on VEGFR2, and consistently it induces endothelial cell proliferation, survival and migration. When added to angiogenic factors (VEGF and/or FGF-2), QK produces an improved biological action, which resulted in reduced apoptosis and accelerated in vitro wound healing. The VEGF-like activity of the short peptide QK, characterized by lower cost of production and easier handling compared to the native glycoprotein, suggests that it is an attractive candidate to be further developed for application in therapeutic angiogenesis.
authors.affiliation: Sezione di Farmacologia, Dipartimento di Biotecnologie, Università degli Studi di Siena, Via A. Moro 2, 53100 Siena, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Finetti
authors.forename: Anna
authors.initials: A
authors.lastname: Basile
authors.forename: Domenica
authors.initials: D
authors.lastname: Capasso
authors.forename: Sonia
authors.initials: S
authors.lastname: Di Gaetano
authors.forename: Rossella
authors.initials: R
authors.lastname: Di Stasi
authors.forename: Maria
authors.initials: M
authors.lastname: Pascale
authors.forename: Caterina Maria
authors.initials: CM
authors.lastname: Turco
authors.forename: Marina
authors.initials: M
authors.lastname: Ziche
authors.forename: Lucia
authors.initials: L
authors.lastname: Morbidelli
authors.forename: Luca Domenico
authors.initials: LD
authors.lastname: D'Andrea
mesh_terms: D000595:Amino Acid Sequence; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology* / Q000502:physiology*
chemical_list: D043925:Angiogenesis Inducing Agents; D010446:Peptide Fragments; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A