Effect of anti-tumor necrosis factor-alpha polyclonal antibody on restenosis after balloon angioplasty in a rabbit atherosclerotic model.
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.
Zhou
Zhongmin
Z
Department of Cardiology, The Cleveland Clinic Foundation, Desk F25, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Lauer
Michael A
MA
Wang
Kai
K
Forudi
Farhad
F
Zhou
Xiaorong
X
Song
Xiao yu
Xy
Solowski
Nancy
N
Kapadia
Samir R
SR
Nakada
Marian T
MT
Topol
Eric J
EJ
Lincoff
A Michael
AM
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
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha