title: Effect of anti-tumor necrosis factor-alpha polyclonal antibody on restenosis after balloon angioplasty in a rabbit atherosclerotic model.
abstract: Inflammation has been postulated to contribute to restenosis after balloon angioplasty. Tumor necrosis factor (TNF)-alpha is a pleiotropic proinflammatory cytokine involved in many features of inflammation. We examined the tissue expression pattern of TNF-alpha and the inflammatory response to arterial injury, and the effects of a goat anti-rabbit-TNF-alpha polyclonal antibody on tissue TNF-alpha expression, inflammation and restenosis in a rabbit atherosclerotic model. At different time points following air dessication and subsequent balloon injury, fresh rabbit femoral artery tissues were homogenized and analyzed for TNF-alpha levels by quantitative TNF-alpha bioassay. Rabbits were treated with a goat anti-rabbit-TNF-alpha polyclonal antibody, Serum and tissue TNF-alpha neutralization, macrophage infiltration (as an indicator of inflammation), and neointimal areas were determined. Balloon angioplasty increased tissue TNF-alpha expression 100000-fold over baseline, and this increase persisted over 6 days after arterial injury, serum anti-TNF-alpha antibody levels were sufficient to neutralize tissue TNF-alpha activity by 60-75%, macrophage infiltration was suppressed, but did not decrease the neointimal formation. These data indicate that tissue TNF-alpha levels were markedly increased after balloon angioplasty. Anti-TNF-alpha treatment was sufficient to neutralize tissue TNF-alpha activity, reduce inflammation, but did not inhibit neointimal formation following balloon angioplasty in a rabbit atherosclerotic model.
authors.affiliation: Department of Cardiology, The Cleveland Clinic Foundation, Desk F25, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Zhou
authors.forename: Michael A
authors.initials: MA
authors.lastname: Lauer
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Farhad
authors.initials: F
authors.lastname: Forudi
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiao yu
authors.initials: Xy
authors.lastname: Song
authors.forename: Nancy
authors.initials: N
authors.lastname: Solowski
authors.forename: Samir R
authors.initials: SR
authors.lastname: Kapadia
authors.forename: Marian T
authors.initials: MT
authors.lastname: Nakada
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000473:pathology*; D006041:Goats; D006083:Graft Occlusion, Vascular / Q000473:pathology*; D006965:Hyperplasia / Q000473:pathology; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*; D017539:Tunica Intima / Q000473:pathology
chemical_list: D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha