title: iNOS Activity Modulates Inflammation, Angiogenesis, and Tissue Fibrosis in Polyether-Polyurethane Synthetic Implants.
abstract: There is considerable interest in implantation techniques and scaffolds for tissue engineering and, for safety and biocompatibility reasons, inflammation, angiogenesis, and fibrosis need to be determined. The contribution of inducible nitric oxide synthase (iNOS) in the regulation of the foreign body reaction induced by subcutaneous implantation of a synthetic matrix was never investigated. Here, we examined the role of iNOS in angiogenesis, inflammation, and collagen deposition induced by polyether-polyurethane synthetic implants, using mice with targeted disruption of the iNOS gene (iNOS(-/-)) and wild-type (WT) mice. The hemoglobin content and number of vessels were decreased in the implants of iNOS(-/-) mice compared to WT mice 14 days after implantation. VEGF levels were also reduced in the implants of iNOS(-/-) mice. In contrast, the iNOS(-/-) implants exhibited an increased neutrophil and macrophage infiltration. However, no alterations were observed in levels of CXCL1 and CCL2, chemokines related to neutrophil and macrophage migration, respectively. Furthermore, the implants of iNOS(-/-) mice showed boosted collagen deposition. These data suggest that iNOS activity controls inflammation, angiogenesis, and fibrogenesis in polyether-polyurethane synthetic implants and that lack of iNOS expression increases foreign body reaction to implants in mice.
authors.affiliation: Laboratório de Angiogênese e Células-Tronco, Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil ; Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Puebla
authors.initials: P
authors.lastname: Cassini-Vieira
authors.affiliation: Laboratório de Angiogênese, Área de Ciências Fisiológicas-ARFIS, Universidade Federal de Uberlândia, 38405-320 Uberlândia, MG, Brazil.
authors.forename: Fernanda Assis
authors.initials: FA
authors.lastname: Araújo
authors.affiliation: Laboratório de Angiogênese e Células-Tronco, Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Filipi Leles
authors.initials: FL
authors.lastname: da Costa Dias
authors.affiliation: Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil ; Laboratório de Imunologia e Mecânica Pulmonar, Departamento de Fisiologia e Biofísica, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Remo Castro
authors.initials: RC
authors.lastname: Russo
authors.affiliation: Laboratório de Angiogênese e Células-Tronco, Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Silvia Passos
authors.initials: SP
authors.lastname: Andrade
authors.affiliation: Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Laboratório de Angiogênese e Células-Tronco, Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil ; Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Luciola Silva
authors.initials: LS
authors.lastname: Barcelos
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D005355:Fibrosis; D007249:Inflammation / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D020556:Neutrophil Infiltration; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*; D011140:Polyurethanes; D019736:Prostheses and Implants
chemical_list: D011140:Polyurethanes; D003094:Collagen; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse