Antagonism of the alpha4 integrin subunit attenuates the acute inflammatory response to stent implantation yet is insufficient to prevent late intimal formation.
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 alpha4 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-alpha4 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.
Ma
Xiaoli
X
Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada K1Y4W7.
O'Brien
Edward R
ER
D000800:Angioplasty, Balloon; D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D006937:Hypercholesterolemia / Q000276:immunology / Q000628:therapy; D007083:Iliac Artery / Q000293:injuries / Q000473:pathology; D039041:Integrin alpha4beta1 / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000276:immunology; D011817:Rabbits; D015607:Stents / Q000009:adverse effects*; D017539:Tunica Intima / Q000293:injuries / Q000473:pathology*; D014657:Vasculitis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D039041:Integrin alpha4beta1