DisBa-01 inhibits angiogenesis, inflammation and fibrogenesis of sponge-induced-fibrovascular tissue in mice

• Published in: Toxicon (Oxford) Vol. 92; pp. 81 - 89
• Main Authors: Cassini-Vieira, Puebla, Deconte, Simone Ramos, Tomiosso, Tatiana Carla, Campos, Paula Peixoto, Montenegro, Cyntia de Freitas, Selistre-de-Araújo, Heloisa Sobreiro, Barcelos, Lucíola Silva, Andrade, Silvia Passos, Araújo, Fernanda de Assis
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15-12-2014
• Subjects: Acetylglucosaminidase - metabolism; Activation; Angiogenesis; Animals; Bothrops - metabolism; Bothrops alternatus; Chemokines; Crotalid Venoms - analysis; Crotalid Venoms - pharmacology; Cytokines; Deposition; Diseases; Disintegrin; Disintegrins - analysis; Disintegrins - pharmacology; Drug Evaluation, Preclinical; Extracellular Matrix - drug effects; Hemoglobin; Imaging; Implants; Inflammation; Inflammation - prevention & control; Laser-Doppler Flowmetry; Macrophages - drug effects; Mice; Neovascularization, Physiologic - drug effects; Peroxidase - metabolism; Polyurethanes; Recombinant; Recombinant Proteins - pharmacology; Regional Blood Flow - drug effects; Angiogenesis; Inflammation; Disintegrin; Cytokines; Chemokines; Implants
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2014.10.007

Integrins are involved in a number of physio-pathological processes including wound healing, chronic inflammation and neoplasias. Blocking its activity is potentially of therapeutic value in these conditions. We investigated whether DisBa-01, a recombinant His-tag RGD-disintegrin from Bothrops alternatus snake venom, could modulate key events (inflammatory cell recruitment/activation, neovascularization and extracellular matrix deposition) of the proliferative fibrovascular tissue induced by polyether polyurethane sponge implants in mice. The hemoglobin content (μg/mg wet tissue), blood flow measurements (laser Doppler perfusion imaging) and number of vessels in the implants, used as indices of vascularization, showed that the disintegrin dose-dependently reduced angiogenesis in the implants relative to the Saline-treated group. DisBa-01 inhibited neutrophil and macrophage content as determined by the myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAG) activities, respectively. Similarly, down regulation of the fibrogenic component studied (collagen deposition) was observed in DisBa-01-treated implants. VEGF, bFGF, TNF-α, CXCL1 and CCL2 levels were also decreased by the disintegrin. The inhibitory effect of this αvβ3-blocking disintegrin on the angiogenic, inflammatory, and fibrogenic components of the fibrovascular tissue induced by the synthetic matrix extends the range of DisBa-01 actions and may indicate its therapeutic potential in controlling angiogenesis in fibroproliferative diseases.
•We evaluated the effects of DisBa-01 on the inflammatory, angiogenic and fibrogenic responses.•DisBa-01 inhibited angiogenesis inflammatory.•DisBa-01 may be therapeutic potential in controlling fibroproliferative diseases.