J Am Coll Cardiol 2001 Aug;38(2):577-82
Prevention of intimal hyperplasia with recombinant soluble P-selectin
glycoprotein ligand-immunoglobulin in the porcine coronary artery
balloon injury model.
Wang K, Zhou Z, Zhou X, Tarakji K, Topol EJ, Lincoff AM.
Department of Cardiology, The Cleveland Clinic Foundation, Ohio 44195, USA.
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. |
