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

作者：Cassini Vieira Puebla; Deconte Simone Ramos; Tomiosso Tatiana Carla; Campos Paula Peixoto; Montenegro Cyntia de Freitas; Selistre de Araujo Heloisa Sobreiro; Barcelos Luciola Silva; Andrade Silvia Passos; Araujo Fernanda de Assis^*

来源：Toxicon, 2014, 92: 81-89.

DOI：10.1016/j.toxicon.2014.10.007

• Disintegrin
• Angiogenesis
• Inflammation
• Implants
• Cytokines
• Chemokines

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 Histag 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 (mu g/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-beta-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-alpha, CXCL1 and CCL2 levels were also decreased by the disintegrin. The inhibitory effect of this alpha(v)beta(3)-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.

• 出版日期2014-12-15