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

Abstract

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 measurement(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.