Modulation of Angiogenesis by a Tetrameric Tripeptide That Antagonizes Vascular Endothelial Growth Factor Receptor(180 visite) Ponticelli S, Marasco D, Tarallo V, Albuquerque RJC, Mitola S, Takeda A, Stassen J, Presta M, Ambati J, Ruvo M, De Falco S
*** IBB - CNR *** Angiogenesis Laboratory and Stem Cell Fate Laboratory, Institute of Genetics and Biophysics Adriano Buzzati-Traverso, Consiglio Nazionale Delle Ricerche (CNR), 80131 Napoli, Italy Institute of Biostructures and Bioimaging, CNR, 80134 Napoli, Italy Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY 40536, United States Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, 25123 Brescia, Italy Thrombogenics, Campus Gasthuisberg, B-3000 Leuven, Belgium
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Vascular endothelial growth factor receptor-1 (VEGFR-1, also known as Flt-1) is involved in complex biological processes often associated to severe pathological conditions like cancer, inflammation, and metastasis formation. Consequently, the search for antagonists of Flt-1 has recently gained a growing interest. Here we report the identification of a tetrameric tripeptide from a combinatorial peptide library built using non-natural amino acids, which binds Flt-1 and inhibits in vitro its interaction with placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) A and B (IC(50) similar to 10 mu M). The peptide is stable in serum for 7 days and prevents both Flt-1 phosphorylation and the capillary-like tube formation of human primary endothelial cells stimulated by PlGF or VEGF-A. Conversely, the identified peptide does not interfere in VEGF-induced VEGFR-2 activation. In vivo, this peptide inhibits VEGF-A- and PlGF-induced neoangiogenesis in the chicken embryo chorioallantoic membrane assay. In contrast, in the cornea, where avascularity is maintained by high levels of expression of the soluble form of Flt-1 receptor (sFlt-1) that prevents the VEGF-A activity, the peptide is able to stimulate corneal mouse neovascularization in physiological condition, as reported previously for others neutralizing anti-Flt-1 molecules. This tetrameric tripeptide represents a new, promising compound for therapeutic approaches in pathologies where Flt-1 activation plays a crucial role.
Schutz K, Alecsandru D, Grimbacher B, Haddock J, Bruining A, Driessen G, De Vries E, Van Hagen PM, Hartmann I, Fraioli F, Milito C, Mitrevski M, Quinti I, Serra G, Kelleher P, Loebinger M, Litzman J, Postranecka V, Thon V, Babar J, Condliffe AM, Exley A, Kumararatne D, Screaton N, Jones A, Bondioni MP, Lougaris V, Plebani A, Soresina A, Sirignano C, Spadaro G, Galal N, Gonzalez-granado LI, Dettmer S, Stirling R, Chapel H, Lucas M, Patel S, Farber CM, Meyts I, Banerjee AK, Hackett S, Hurst JR, Warnatz K, Gathmann B, Weidemann J, Berthold D, Baumann U * Correction to: Imaging of Bronchial Pathology in Antibody Deficiency: Data from the European Chest CT Group(35 visite) J Clin Immunol (ISSN: 0271-9142linking), 2019 Feb; 39(2): 225-227. Impact Factor:2.654 DettagliEsporta in BibTeXEsporta in EndNote
Schutz K, Alecsandru D, Grimbacher B, Haddock J, Bruining A, Driessen G, De Vries E, Van Hagen PM, Hartmann I, Fraioli F, Milito C, Mitrevski M, Quinti I, Serra G, Kelleher P, Loebinger M, Litzman J, Postranecka V, Thon V, Babar J, Condliffe AM, Exley A, Kumararatne D, Screaton N, Jones A, Bondioni MP, Lougaris V, Plebani A, Soresina A, Sirignano C, Spadaro G, Galal N, Gonzalez-granado LI, Dettmer S, Stirling R, Chapel H, Lucas M, Patel S, Farber CM, Meyts I, Banerjee AK, Hackett S, Hurst JR, Warnatz K, Gathmann B, Weidemann J, Berthold D, Baumann U, Schutz K, Alecsandru D, Grimbacher B, Haddock J, Bruining A, Driessen G, De Vries E, Van Hagen PM, Hartmann I, Fraioli F, Milito C, Mitrevski M, Quinti I, Serra G, Kelleher P, Loebinger M, Litzman J, Postranecka V, Thon V, Babar J, Condliffe AM, Exley A, Kumararatne D, Screaton N, Jones A, Bondioni MP, Lougaris V, Plebani A, Soresina A, Sirignano C, Spadaro G, Galal N, Gonzalez-granado LI, Dettmer S, Stirling R, Chapel H, Lucas M, Patel S, Farber CM, Meyts I, B Imaging of Bronchial Pathology in Antibody Deficiency: Data from the European Chest CT Group(49 visite) J Clin Immunol (ISSN: 0271-9142linking, 1573-2592), 2019 Jan; 3939(2): 45-54. Impact Factor:2.654 DettagliEsporta in BibTeXEsporta in EndNote
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773 Records (724 escludendo Abstract e Conferenze). Impact factor totale: 2665.606 (2523.403 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 2789.786 (2634.965 escludendo Abstract e Conferenze).