title: DisBa-01 inhibits angiogenesis, inflammation and fibrogenesis of sponge-induced-fibrovascular tissue in mice.
abstract: 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.
authors.affiliation: Departamento de Ciências Fisiológicas - ARFIS, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors.forename: Puebla
authors.initials: P
authors.lastname: Cassini-Vieira
authors.affiliation: Instituto de Genética e Bioquímica - INGEB, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors.forename: Simone Ramos
authors.initials: SR
authors.lastname: Deconte
authors.affiliation: Departamento de Morfologia - ARMOR, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors.forename: Tatiana Carla
authors.initials: TC
authors.lastname: Tomiosso
authors.affiliation: Departamento de Patologia, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil.
authors.forename: Paula Peixoto
authors.initials: PP
authors.lastname: Campos
authors.affiliation: Departamento de Ciências Fisiológicas - DCF, Universidade Federal de São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Cyntia de Freitas
authors.initials: Cde F
authors.lastname: Montenegro
authors.affiliation: Departamento de Ciências Fisiológicas - DCF, Universidade Federal de São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Heloisa Sobreiro
authors.initials: HS
authors.lastname: Selistre-de-Araújo
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto Nacional de Ciência e Tecnologia (INCT-NanoBiofar), Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Lucíola Silva
authors.initials: LS
authors.lastname: Barcelos
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto Nacional de Ciência e Tecnologia (INCT-NanoBiofar), Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Silvia Passos
authors.initials: SP
authors.lastname: Andrade
authors.affiliation: 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.
authors.forename: Fernanda de Assis
authors.initials: Fde A
authors.lastname: Araújo
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D017837:Bothrops / Q000378:metabolism*; D003435:Crotalid Venoms / Q000032:analysis* / Q000494:pharmacology; D019483:Disintegrins / Q000032:analysis / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005109:Extracellular Matrix / Q000187:drug effects*; D007249:Inflammation / Q000517:prevention & control*; D017078:Laser-Doppler Flowmetry; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D011140:Polyurethanes; D011994:Recombinant Proteins / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D003435:Crotalid Venoms; C000599692:DisBa-01, Bothrops alternatus; D019483:Disintegrins; D011140:Polyurethanes; D011994:Recombinant Proteins; C115016:polyetherurethane; D009195:Peroxidase; D000118:Acetylglucosaminidase
keywords: Angiogenesis; Chemokines; Cytokines; Disintegrin; Implants; Inflammation