title: Nitric oxide modulates metalloproteinase-2, collagen deposition and adhesion rate after polypropylene mesh implantation in the intra-abdominal wall.
abstract: Prosthetic meshes are commonly used to correct abdominal wall defects. However, the inflammatory reaction induced by these devices in the peritoneum is not completely understood. We hypothesized that nitric oxide (NO), produced by nitric oxide synthase 2 (NOS2) may modulate the response induced by mesh implants in the abdominal wall and, consequently, affect the outcome of the surgical procedure. Polypropylene meshes were implanted in the peritoneal side of the abdominal wall in wild-type and NOS2-deficient (NOS2(-/-)) mice. After 15 days tissues around the mesh implant were collected, and inflammatory markers (the cytokine interleukin 1β (IL-1β) and NO) and tissue remodeling (collagen and metalloproteinases (MMP) 2 and 9) were analyzed. The lack of NOS2-derived NO induced a higher incidence of visceral adhesions at the mesh implantation site compared with wild-type mice that underwent the same procedure (P<0.05). Additionally, higher levels of IL-1β were present in the mesh-implanted NOS2(-/-) animals compared with control and wild-type mice. Mesh implantation induced collagen I and III deposition, but in smaller amounts in NOS2(-/-) mice. MMP-9 activity after the surgical procedure was similarly increased in both groups. Conversely, MMP-2 activity was unchanged in mesh-implanted wild-type mice, but was significantly increased in NOS2(-/-) mice (P<0.01), due to decreased S-nitrosylation of the enzyme in these animals. We conclude that NOS2-derived NO is crucial for an adequate response to and integration of polypropylene mesh implants in the peritoneum. NO deficiency results in a prolonged inflammatory reaction to the mesh implant, and reduced collagen deposition may contribute to an increased incidence of visceral adhesions.
authors.affiliation: Emergency Medicine Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. aismoretti@yahoo.com.br
authors.forename: Ana I S
authors.initials: AI
authors.lastname: Moretti
authors.forename: Francisco J P Souza
authors.initials: FJ
authors.lastname: Pinto
authors.forename: Vivian
authors.initials: V
authors.lastname: Cury
authors.forename: Marcia C
authors.initials: MC
authors.lastname: Jurado
authors.forename: Wagner
authors.initials: W
authors.lastname: Marcondes
authors.forename: Irineu T
authors.initials: IT
authors.lastname: Velasco
authors.forename: Heraldo P
authors.initials: HP
authors.lastname: Souza
mesh_terms: D034861:Abdominal Wall / Q000473:pathology / Q000601:surgery*; D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008422:Materials Testing; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011126:Polypropylenes / Q000378:metabolism*; D019736:Prostheses and Implants; D011897:Random Allocation; D013526:Surgical Mesh; D000267:Tissue Adhesions / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing / Q000502:physiology
chemical_list: D001672:Biocompatible Materials; D053583:Interleukin-1beta; D011126:Polypropylenes; D009569:Nitric Oxide; D003094:Collagen; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9