Effects of Blocking αvβ₃ integrin by a recombinant RGD disintegrin on remodeling of wound healing after induction of incisional hernia in rats

Acta Cir Bras. 2014:29 Suppl 3:6-13. doi: 10.1590/s0102-86502014001700002.

Abstract

Purpose: Incisional hernia (IH) is characterized by defective wound healing process. Disba-01, a αvb₃ integrin blocker has shown to control the rate of wound repair and therefore it could be a target for new wound healing therapies.The objective of the study was to determine the changes induced by Disba-01 on repair of wound healing after induced IH in rats.

Methods: Thirty two male albino rats were submitted to IH and divided into 4 experimental groups: G1, placebo control; G2, DisBa-01-treated; G3, anti-αvβ₃ antibodies-treated and G4, anti-α₂ antibodies-treated. Histological. biochemical and extracellular matrix remodeling analysis of abdominal wall were evaluated.

Results: After 14 days, 100% of the G2 did not present hernia, and the hernia ring was closed by a thin membrane. In contrast, all groups maintained incisional hernia. DisBa-01 also increased the number macrophages and fibroblasts and induced the formation of new vessels. Additionally, MMP-2 was strongly activated only in G2 (P<0.05). Anti- αvβ₃-integrin antibodies produced similar results than Disba-01 but not anti-α₂ integrin blocking antibodies.

Conclusion: These results strongly indicate that Disba-01 has an important role in the control of wound healing and the blocking of this integrin may be an interesting therapeutical strategy in IH.

MeSH terms

  • Abdominal Wall*
  • Animals
  • Collagen / drug effects
  • Disintegrins / pharmacology*
  • Fibroblasts / drug effects
  • Hernia, Ventral / drug therapy*
  • Hernia, Ventral / metabolism
  • Integrin alphaVbeta3 / antagonists & inhibitors*
  • Integrin alphaVbeta3 / chemistry
  • Integrin alphaVbeta3 / metabolism
  • Macrophages / drug effects
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 2 / pharmacology*
  • Postoperative Complications / prevention & control
  • Random Allocation
  • Rats, Wistar
  • Wound Healing / drug effects*
  • Wound Healing / physiology

Substances

  • Disintegrins
  • Integrin alphaVbeta3
  • Collagen
  • Matrix Metalloproteinase 2