Role of vascular endothelial growth factor and placental growth factor in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic mice.
OBJECTIVE
To evaluate the role of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in adhesion formation after laparoscopic surgery.


METHODS
Prospective, randomized study.


METHODS
Academic research center.


METHODS
Female wild-type mice and transgenic mice (n = 110), expressing exclusively VEGF-A(164) (VEGF-A(164/164)) or deficient for VEGF-B (VEGF-B(-/-)) or for PlGF (PlGF(-/-)).


METHODS
Adhesions were induced during laparoscopy. To evaluate "basal adhesions" and "CO(2) pneumoperitoneum-enhanced adhesions," the pneumoperitoneum was maintained for a minimum (10 minutes) or prolonged (60 minutes) period. The role of PlGF was also evaluated by administration of antibodies.


METHODS
Adhesions were blindly scored after 7 days.


RESULTS
In all wild-type mice, CO(2) pneumoperitoneum enhanced adhesion formation. In comparison with wild-type mice, basal adhesions were higher in VEGF-A(164/164) mice and similar in VEGF-B(-/-) and PlGF(-/-) mice. Pneumoperitoneum did not enhance adhesions in any of these transgenic mice. The effects observed in PlGF(-/-) mice were confirmed in PlGF antibody-treated mice.


CONCLUSIONS
The data demonstrate that the VEGF family plays a role in adhesion formation and confirm that CO(2) pneumoperitoneum enhances adhesions. VEGF-A(164) has a direct role in basal adhesions. Absence of pneumoperitoneum-enhanced adhesions in VEGF-A(164/164), VEGF-B(-/-), and PlGF(-/-) mice indicates up-regulation of VEGF-A(164), VEGF-B, and PlGF by CO(2) pneumoperitoneum as a mechanism for pneumoperitoneum-enhanced adhesion formation.
D000818:Animals; D002245:Carbon Dioxide / Q000009:adverse effects; D016228:Endothelial Growth Factors / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D010535:Laparoscopy / Q000009:adverse effects*; D008222:Lymphokines / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010537:Peritoneum / Q000601:surgery*; D000072483:Placenta Growth Factor; D011028:Pneumoperitoneum, Artificial / Q000009:adverse effects*; D011183:Postoperative Complications; D011257:Pregnancy Proteins / Q000502:physiology*; D011446:Prospective Studies; D011897:Random Allocation; D000267:Tissue Adhesions / Q000209:etiology* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D002245:Carbon Dioxide; D000072483:Placenta Growth Factor