iNOS Activity Modulates Inflammation, Angiogenesis, and Tissue Fibrosis in Polyether-Polyurethane Synthetic Implants

Author:

Cassini-Vieira Puebla12,Araújo Fernanda Assis3,da Costa Dias Filipi Leles1,Russo Remo Castro24,Andrade Silvia Passos1,Teixeira Mauro Martins2,Barcelos Luciola Silva12

Affiliation:

1. Laboratório de Angiogênese e Células-Tronco, Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil

2. Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil

3. Laboratório de Angiogênese, Área de Ciências Fisiológicas-ARFIS, Universidade Federal de Uberlândia, 38405-320 Uberlândia, MG, Brazil

4. Laboratório de Imunologia e Mecânica Pulmonar, Departamento de Fisiologia e Biofísica, 31270-901 Belo Horizonte, MG, Brazil

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.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Publisher

Hindawi Limited

Subject

Cell Biology,Immunology

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