PT - JOURNAL ARTICLE AU - Rezzola, Sara AU - Dal Monte, Massimo AU - Belleri, Mirella AU - Bugatti, Antonella AU - Chiodelli, Paola AU - Corsini, Michela AU - Cammalleri, Maurizio AU - Cancarini, Anna AU - Morbidelli, Lucia AU - Oreste, Pasqua AU - Bagnoli, Paola AU - Semeraro, Francesco AU - Presta, Marco TI - Therapeutic Potential of Anti-Angiogenic Multitarget <em>N,O</em>-Sulfated <em>E. Coli</em> K5 Polysaccharide in Diabetic Retinopathy AID - 10.2337/db14-1378 DP - 2015 Jul 01 TA - Diabetes PG - 2581--2592 VI - 64 IP - 7 4099 - http://diabetes.diabetesjournals.org/content/64/7/2581.short 4100 - http://diabetes.diabetesjournals.org/content/64/7/2581.full SO - Diabetes2015 Jul 01; 64 AB - Vascular endothelial growth factor (VEGF) blockers have been developed for the treatment of proliferative diabetic retinopathy (PDR), the leading cause of visual impairments in the working-age population in the Western world. However, limitations to anti-VEGF therapies may exist because of the local production of other proangiogenic factors that may cause resistance to anti-VEGF interventions. Thus, novel therapeutic approaches targeting additional pathways are required. Here, we identified a sulfated derivative of the Escherichia coli polysaccharide K5 [K5-N,OS(H)] as a multitarget molecule highly effective in inhibiting VEGF-driven angiogenic responses in different in vitro, ex vivo, and in vivo assays, including a murine model of oxygen-induced retinopathy. Furthermore, K5-N,OS(H) binds a variety of heparin-binding angiogenic factors upregulated in PDR vitreous humor besides VEGF, thus inhibiting their biological activity. Finally, K5-N,OS(H) hampers the angiogenic activity exerted in vitro and in vivo by human vitreous fluid samples collected from patients with PDR. Together, the data provide compelling experimental evidence that K5-N,OS(H) represents an antiangiogenic multitarget molecule with potential implications for the therapy of pathologic neovessel formation in the retina of patients with PDR.