Antagonism of the α4 integrin subunit attenuates the acute inflammatory response to stent implantation yet is insufficient to prevent late intimal formation

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Abstract
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 α4 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-α4 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.
Funding Information
  • Ann Fook Yang from Agriculture Canada
  • Heart and Stroke Foundation of Ontario and the Canadian Institutes of Health Research
  • Canadian Institute of Health Research-University Industry Investigator