Adenovirus-mediated overexpression of human tissue plasminogen activator prevents peritoneal adhesion formation/reformation in rats

Hussein M. Atta, Ayman Al-Hendy, Mahmoud A. El-Rehany, Mieke Dewerchin, Salama R. Abdel Raheim, Hend Abdel Ghany, Rasha Fouad

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11 Scopus citations

Abstract

Background: Tissue-plasminogen activator (tPA) demonstrated beneficial effects on peritoneal adhesion formation; however, its short half-life limits its continual fibrinolytic effect. Therefore, we delivered adenovirus encoding tPA to prevent adhesions. Methods: Rats were subjected to peritoneal injury and assigned to two protocols. In de novo adhesion protocol, adenovirus encoding human tPA gene (Ad-htPA) was instilled after peritoneal injury in group1 (n = 22), whereas group 2 received phosphate-buffered saline (PBS) (n = 24). In recurrent adhesion protocol, group 1 (n = 15) received the same Ad-htPA dose after adhesiolysis and group 2 (n = 13) received PBS. Adhesion severity was scored 1 week after ad-htPA instillation. Adhesions were analyzed for htPA mRNA by reverse transcription-polymerase chain reaction and levels of htPA, and fibrinolytic inhibitors PAI-1, TIMP-1, and TGF-β1 were measured using enzyme-linked immunosorbent assay. Results: htPA mRNA and protein were only expressed in adhesions from treated groups. A reduction in adhesion scores (P < .01) and in fibrinolytic inhibitors (P < .001) occurred in the treatment groups. Also, negative correlation was found (r = -.69, P < .01) between adhesion scores and htPA protein, but a positive correlation was found (r = .90, P < .01) between adhesion score and fibrinolytic inhibitors. No bleeding or wound complications were encountered. Conclusion: Administration of adenovector encoding htPA is safe and decreased de novo and recurrent peritoneal adhesions.

Original languageEnglish (US)
Pages (from-to)12-17
Number of pages6
JournalSurgery
Volume146
Issue number1
DOIs
StatePublished - Jul 2009

ASJC Scopus subject areas

  • Surgery

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