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

Fertil Steril. 2003 Sep:80 Suppl 2:803-11. doi: 10.1016/s0015-0282(03)00768-4.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Dioxide / adverse effects
  • Endothelial Growth Factors / physiology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Laparoscopy / adverse effects*
  • Lymphokines / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peritoneum / surgery*
  • Placenta Growth Factor
  • Pneumoperitoneum, Artificial / adverse effects*
  • Postoperative Complications
  • Pregnancy Proteins / physiology*
  • Prospective Studies
  • Random Allocation
  • Tissue Adhesions / etiology*
  • Tissue Adhesions / metabolism
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Pgf protein, mouse
  • Pregnancy Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Carbon Dioxide
  • Placenta Growth Factor