Intraperitoneal administration of activated protein C prevents postsurgical adhesion band formation. Blood 2015 Feb 19;125(8):1339-48
Date
01/13/2015Pubmed ID
25575539Pubmed Central ID
PMC4335085DOI
10.1182/blood-2014-10-609339Scopus ID
2-s2.0-84923378695 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
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.
Author List
Dinarvand P, Hassanian SM, Weiler H, Rezaie ARAuthor
Hartmut Weiler PhD Associate Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCytokines
Drug Evaluation, Preclinical
Inflammation
Inflammation Mediators
Infusions, Parenteral
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Peritoneal Diseases
Peritonitis
Postoperative Complications
Protein C
Tissue Adhesions
