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
Fertility and Sterility vol:80 Suppl 2 pages:803-11
OBJECTIVE: To evaluate the role of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in adhesion formation after laparoscopic surgery. DESIGN: Prospective, randomized study. SETTING: Academic research center. ANIMAL(S): 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(-/-)). INTERVENTION(S): 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. MAIN OUTCOME MEASURE(S): Adhesions were blindly scored after 7 days. RESULT(S): 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. CONCLUSION(S): 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.