(Circulation. 2001;103:1906.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Selective 
vß3-Receptor Blockade Reduces Macrophage Infiltration and Restenosis After Balloon Angioplasty in the Atherosclerotic Rabbit
From the University of Virginia, Charlottesville, Va (G.G.B., J.A.M., J.M.S., S.E.H., M.J.F., C.A.M., L.W.G., E.R.P., I.J.S.), and DuPont Pharmaceutical Company, Wilmington, Del (S.A.M.).
Correspondence to Ian J. Sarembock, MD, Cardiovascular Division, University of Virginia Health System, Box 158, Charlottesville, VA 22908. E-mail ijs4s{at}virginia.edu
Background—
vß3-Integrin
receptors are upregulated in atherosclerotic arteries and play a key
role in smooth muscle cell and possibly inflammatory cell
migration. We hypothesized that after balloon angioplasty (BA)
of atherosclerotic arteries, selective inhibition of the
vß3-receptor by
XT199, a small-molecule, non–peptide-selective
vß3-receptor
antagonist, would reduce restenosis.
Methods and Results—After induction of focal atherosclerosis, rabbits underwent femoral BA and received XT199 (2.5 mg/kg IV bolus plus 2.5 mg · kg-1 · d-1 IV; n=19) or vehicle (n=20) for 14 days. At 28 days after BA, the XT199 group had a larger lumen (0.75±0.26 versus 0.57±0.20 mm2, P=0.03) and a smaller neointimal area (0.49±0.18 versus 0.68±0.25 mm2, P=0.01) than the vehicle group. Angiographic analysis confirmed a 30% to 40% reduction in restenosis. Arteries harvested at 28 days after BA did not show a reduction in intima plus media smooth muscle cell content but did show a 50% reduction in macrophage cell density in the XT199 group (716±452 versus 1458±989 cells/mm2, P<0.006). Neovessel density at 28 days was also reduced (23±42 versus 58±46 vessel cross sections/mm2, P<0.02). Early after BA (ie, 3 to 7 days), there was a decrease in intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, indicative of a reduction in vascular cell activation.
Conclusions—Selective
vß3-receptor
blockade for 14 days after BA in the focally atherosclerotic rabbit
significantly reduced restenosis and limited macrophage infiltration
and neovascularization in the vessel
wall.
Key Words: restenosis • angioplasty • inflammation • drugs
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