TY - JOUR
T1 - Adenovirus-mediated overexpression of human tissue plasminogen activator prevents peritoneal adhesion formation/reformation in rats
AU - Atta, Hussein M.
AU - Al-Hendy, Ayman
AU - El-Rehany, Mahmoud A.
AU - Dewerchin, Mieke
AU - Abdel Raheim, Salama R.
AU - Ghany, Hend Abdel
AU - Fouad, Rasha
N1 - Funding Information:
Supported by the U.S.–Egypt Science and Technology Joint Fund in cooperation with the University of Texas Medical Branch at Galveston and Minia University under Project BIO9-005-001.
PY - 2009/7
Y1 - 2009/7
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=67249164542&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67249164542&partnerID=8YFLogxK
U2 - 10.1016/j.surg.2009.02.018
DO - 10.1016/j.surg.2009.02.018
M3 - Article
C2 - 19541005
AN - SCOPUS:67249164542
SN - 0039-6060
VL - 146
SP - 12
EP - 17
JO - Surgery
JF - Surgery
IS - 1
ER -