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-A₁₆₄ (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 “CO₂ 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, CO₂ 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 CO₂ pneumoperitoneum enhances adhesions. VEGF-A₁₆₄ 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-A₁₆₄, VEGF-B, and PlGF by CO₂ pneumoperitoneum as a mechanism for pneumoperitoneum-enhanced adhesion formation.