Inducible nitric oxide synthase inhibition increases MMP-2 activity leading to imbalance between extracellular matrix deposition and degradation after polypropylene mesh implant

Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPSOUZA-PINTO, Franciso J. P.MORETTI, Ana I. S.CURY, VivianMARCONDES, WagnerVELASCO, Irineu T.SOUZA, Heraldo P.2013-09-232013-09-232013JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, v.101A, n.5, p.1379-1387, 20131549-3296https://observatorio.fm.usp.br/handle/OPI/1728Prosthetic mesh implants are commonly used to correct abdominal wall defects. However, success of the procedure is conditioned by an adequate inflammatory response to the device. We hypothesized that nitric oxide produced by nitric oxide synthase 2 (NOS2) and MMP-2 and -9 participate in response induced by mesh implants in the abdominal wall and, consequently, affect the outcome of the surgical procedure. In the first step, temporal inflammatory markers profile was evaluated. Polypropylene meshes were implanted in the peritoneal side of the abdominal wall of C57Black mice. After 2, 4, 7, 15, and 30 days, tissues around the mesh implant were collected and inflammatory markers were analyzed. In the second step, NOS2 activity was inhibited with nitro-L-arginine methyl ester (L-NAME). Samples were collected after 15 days (when inflammation was reduced), and the inflammatory and tissue remodeling markers were investigated. Polypropylene mesh implant induced a pro-inflammatory environment mediated by intense MMP-2 and -9 activities, NO release, and interleukin-1 production peaking in 7 days and gradually decreasing after 15 days. NOS2 inhibition increased MMP-2 activity and resulted in a higher visceral adhesion incidence at the mesh implantation site when compared with non-treated animals that underwent the same procedure. We conclude that NOS2-derived NO is crucial for adequate response to polypropylene mesh implant integration in the peritoneum. NO deficiency results in an imbalance between extracellular matrix deposition/degradation contributing to visceral adhesions incidence. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.engrestrictedAccesspolypropylene meshinflammationinducible nitric oxide synthasenitric oxidematrix metalloproteinasesforeign-body reactions-nitrosylationhernia repairmetalloproteinasescollagencellsmodelbiomaterialsmacrophagessepsisInducible nitric oxide synthase inhibition increases MMP-2 activity leading to imbalance between extracellular matrix deposition and degradation after polypropylene mesh implantarticleCopyright WILEY-BLACKWELL10.1002/jbm.a.34440Engineering, BiomedicalMaterials Science, Biomaterials