title: Intraperitoneal administration of activated protein C prevents postsurgical adhesion band formation.
abstract: Postsurgical peritoneal adhesion bands are the most important causes of intestinal obstruction, pelvic pain, and female infertility. In this study, we used a mouse model of adhesion and compared the protective effect of activated protein C (APC) to that of the Food and Drug Administration-approved antiadhesion agent, sodium hyaluronate/carboxymethylcellulose (Seprafilm) by intraperitoneal administration of either APC or Seprafilm to experimental animals. Pathological adhesion bands were graded on day 7, and peritoneal fluid concentrations of tissue plasminogen activator (tPA), d-dimer, thrombin-antithrombin complex, and cytokines (IL-1β, IL-6, interferon-γ, tumor necrosis factor-α, transforming growth factor-β1) were evaluated. Inflammation scores were also measured based on histologic data obtained from peritoneal tissues. Relative to Seprafilm, intraperitoneal administration of human APC led to significantly higher reduction of postsurgical adhesion bands. Moreover, a markedly lower inflammation score was obtained in the adhesive tissues of the APC-treated group, which correlated with significantly reduced peritoneal concentrations of proinflammatory cytokines and an elevated tPA level. Further studies using variants of human APC with or without protease-activated receptor 1 (PAR1) signaling function and mutant mice deficient for either endothelial protein C receptor (EPCR) or PAR1 revealed that the EPCR-dependent signaling activity of APC is primarily responsible for its protective activity in this model. These results suggest APC has therapeutic potential for preventing postsurgical adhesion bands.
authors.affiliation: Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, Saint Louis, MO; and.
authors.forename: Peyman
authors.initials: P
authors.lastname: Dinarvand
authors.affiliation: Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, Saint Louis, MO; and.
authors.forename: Seyed Mahdi
authors.initials: SM
authors.lastname: Hassanian
authors.affiliation: Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Weiler
authors.affiliation: Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, Saint Louis, MO; and.
authors.forename: Alireza R
authors.initials: AR
authors.lastname: Rezaie
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007263:Infusions, Parenteral; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010532:Peritoneal Diseases / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D010538:Peritonitis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D011183:Postoperative Complications / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D011486:Protein C / Q000008:administration & dosage*; D000267:Tissue Adhesions / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D011486:Protein C