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Published online before print March 12, 2004

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(Journal of Leukocyte Biology. 2004;75:1016-1021.)
© 2004 by Society for Leukocyte Biology

Antagonism of the 4 integrin subunit attenuates the acute inflammatory response to stent implantation yet is insufficient to prevent late intimal formation

Vascular Biology Laboratory, Division of Cardiology, University of Ottawa Heart Institute, Ontario, Canada

¹ Correspondence: Vascular Biology Laboratory, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada K1Y4W7. E-mail: eobrien{at}ottawaheart.ca

Mononuclear leukocytes infiltrate the artery wall via integrin-mediated mechanisms and play an integral role in intimal formation after stenting. We sought to determine if acute antagonism of the 4 subunit of very late antigen-4 is sufficient for the late attenuation of stent intimal area (IA). Twenty-four hypercholesterolemic rabbits underwent iliac artery balloon injury, followed 2 weeks later by stent implantation, and the animals were randomized to receive an anti-4 antibody (HP1/2) or a nonspecific isotypic control immunoglobulin (1E6) intravenously 1 h before stenting. Compared with controls, HP1/2-treated rabbits showed 50%, 51%, and 44% reductions in the percentage on intimal cells that were macrophages on days 3, 7, and 28 after stenting and a 59% reduction in intimal proliferation on day 3. Although stent IA was reduced by 63% and 48% in the antibody-treated group compared with the control group on days 3 and 7, this difference was not present on day 28. These data highlight the need for sustained, anti-inflammatory therapies for the prevention of stent intimal formation.

Key Words: restenosis • leukocyte • adhesion

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