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

Research output: Contribution to journalArticle

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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 1 2009

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Tissue Plasminogen Activator
Adenoviridae
Human Adenoviruses
Wounds and Injuries
Phosphates
Messenger RNA
Tissue Inhibitor of Metalloproteinase-1
Plasminogen Activator Inhibitor 1
Genes
Reverse Transcription
Half-Life
Proteins
Enzyme-Linked Immunosorbent Assay
Hemorrhage
Polymerase Chain Reaction
Therapeutics

ASJC Scopus subject areas

  • Surgery

Cite this

Atta, H. M., Al-Hendy, A., El-Rehany, M. A., Dewerchin, M., Abdel Raheim, S. R., Ghany, H. A., & Fouad, R. (2009). Adenovirus-mediated overexpression of human tissue plasminogen activator prevents peritoneal adhesion formation/reformation in rats. Surgery, 146(1), 12-17. https://doi.org/10.1016/j.surg.2009.02.018

Adenovirus-mediated overexpression of human tissue plasminogen activator prevents peritoneal adhesion formation/reformation in rats. / Atta, Hussein M.; Al-Hendy, Ayman; El-Rehany, Mahmoud A.; Dewerchin, Mieke; Abdel Raheim, Salama R.; Ghany, Hend Abdel; Fouad, Rasha.

In: Surgery, Vol. 146, No. 1, 01.07.2009, p. 12-17.

Research output: Contribution to journalArticle

Atta, HM, Al-Hendy, A, El-Rehany, MA, Dewerchin, M, Abdel Raheim, SR, Ghany, HA & Fouad, R 2009, 'Adenovirus-mediated overexpression of human tissue plasminogen activator prevents peritoneal adhesion formation/reformation in rats', Surgery, vol. 146, no. 1, pp. 12-17. https://doi.org/10.1016/j.surg.2009.02.018
Atta, Hussein M. ; Al-Hendy, Ayman ; El-Rehany, Mahmoud A. ; Dewerchin, Mieke ; Abdel Raheim, Salama R. ; Ghany, Hend Abdel ; Fouad, Rasha. / Adenovirus-mediated overexpression of human tissue plasminogen activator prevents peritoneal adhesion formation/reformation in rats. In: Surgery. 2009 ; Vol. 146, No. 1. pp. 12-17.
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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.",
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AU - Dewerchin, Mieke

AU - Abdel Raheim, Salama R.

AU - Ghany, Hend Abdel

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AB - 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.

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