Toxicon. 2014 Dec 15;92:81-9. doi: 10.1016/j.toxicon.2014.10.007. Epub 2014 Oct 15.
DisBa-01 inhibits angiogenesis, inflammation and fibrogenesis of sponge-induced-fibrovascular tissue in mice.
Cassini-Vieira P1, Deconte SR2, Tomiosso TC3, Campos PP4, Montenegro Cde F5, Selistre-de-Araújo HS5, Barcelos LS6, Andrade SP6, Araújo Fde A7.
Departamento de Ciências Fisiológicas - ARFIS, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil.
Instituto de Genética e Bioquímica - INGEB, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil.
Departamento de Morfologia - ARMOR, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil.
Departamento de Patologia, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil.
Departamento de Ciências Fisiológicas - DCF, Universidade Federal de São Carlos, São Carlos, São Paulo, Brazil.
Departamento de Fisiologia e Biofísica, Instituto Nacional de Ciência e Tecnologia (INCT-NanoBiofar), Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Departamento de Ciências Fisiológicas - ARFIS, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil; Departamento de Ciências Fisiológicas - ARFIS, Instituto Nacional de Ciência e Tecnologia (INCT-NanoBiofar), Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil. Electronic address: folaraujo@gmail.com.
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.