Prevention of intimal hyperplasia with recombinant soluble P-selectin glycoprotein ligand-immunoglobulin in the porcine coronary artery balloon injury model

J Am Coll Cardiol. 2001 Aug;38(2):577-82. doi: 10.1016/s0735-1097(01)01347-x.


Objectives: The role of P-selectin in the process of restenosis was evaluated using a recombinant immunoglobulin (Ig) chimera form of its ligand, soluble P-selectin glycoprotein ligand-Ig (rPSGL-Ig), as a competitive inhibitor for the natural ligand on leukocytes.

Background: Inflammation and coagulation activation after vascular injury may be an important factor in the development of restenosis. P-selectin has been shown to mediate leukocyte-endothelium and leukocyte-platelet interaction. These interactions are mediated through binding of P-selectin to P-selectin glycoprotein ligand-1 (PSGL-1) located on the surface of leukocytes.

Methods: Balloon injury was induced in the left anterior descending and right coronary arteries of 16 pigs at a balloon/artery diameter ratio of 1.5:1. Either rPSGL-Ig (1 mg/kg) or saline was randomly administered 15 min before balloon injury as an intravenous bolus. Four weeks after injury, morphometric analysis, immunohistochemistry and histological evaluation were performed on injured arterial segments.

Results: Increased luminal area was found in the rPSGL-Ig group compared with the placebo group (1.63 +/- 0.57 mm2 vs. 1.26 +/- 0.32 mm2, p = 0.044) owing to significantly reduced neointimal hyperplasia (cross-sectional area, 0.46 +/- 0.45 mm2 vs. 0.13 +/- 0.11 mm2, p = 0.013). Immunohistochemistry and histological evaluation showed a significant decrease in the presence of tumor necrosis factor-alpha, interleukin-1 beta, and infiltration of macrophages in the injured vessel segments in the rPSGL-Ig group.

Conclusions: P-selectin antagonism using rPSGL-Ig decreases neointimal hyperplasia following balloon injury, by inhibiting the inflammatory and thrombotic responses at the site of balloon injury, which appears to play a pivotal role in the pathogenesis of restenosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioplasty, Balloon / adverse effects*
  • Animals
  • Coronary Disease / etiology
  • Coronary Disease / pathology
  • Coronary Disease / prevention & control*
  • Hyperplasia / metabolism
  • Hyperplasia / pathology
  • Hyperplasia / prevention & control
  • Immunoglobulins / genetics
  • Immunohistochemistry
  • Interleukin-1 / immunology
  • Interleukin-1 / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / pharmacology*
  • P-Selectin / physiology*
  • Recombinant Fusion Proteins / pharmacology
  • Swine
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism


  • Immunoglobulins
  • Interleukin-1
  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha