RT Journal Article
SR Electronic
T1 Therapeutic Potential of Anti-Angiogenic Multitarget <em>N,O</em>-Sulfated <em>E. Coli</em> K5 Polysaccharide in Diabetic Retinopathy
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 2581
OP 2592
DO 10.2337/db14-1378
VO 64
IS 7
A1 Rezzola, Sara
A1 Dal Monte, Massimo
A1 Belleri, Mirella
A1 Bugatti, Antonella
A1 Chiodelli, Paola
A1 Corsini, Michela
A1 Cammalleri, Maurizio
A1 Cancarini, Anna
A1 Morbidelli, Lucia
A1 Oreste, Pasqua
A1 Bagnoli, Paola
A1 Semeraro, Francesco
A1 Presta, Marco
YR 2015
UL http://diabetes.diabetesjournals.org/content/64/7/2581.abstract
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.