TY - JOUR
T1 - Intracoronary β-irradiation enhances balloon-injury-induced tissue factor expression in the porcine injury model
AU - Finkelstein, Ariel
AU - Hausleiter, Joerg
AU - Doherty, Terence M.
AU - Takizawa, Kaname
AU - Bergman, Jonathan
AU - Liu, Ming
AU - Rukshin, Vladimir
AU - Fishbein, Michael C.
AU - Eigler, Neal
AU - Shah, Prediman K.
AU - Rajavashisth, Tripathi B.
AU - Makkar, Raj R.
N1 - Funding Information:
Supported by grants (HL-51980 and HL-58555 to TBR) from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, Philip Morris USA Inc. (to TBR), the American Heart Association, Dallas, TX (Grant-in-Aid to RRM), and the Lilian Goldstein Save-a Heart Foundation, Los Angeles, CA (to AF). We gratefully acknowledge the generous support of the Mirisch Foundation, United Hostesses' Charities, the Eisner Foundation, the Grand Foundation, Ornest Family Foundation, the Steinberg Foundation, and the Heart Fund at Cedars-Sinai Medical Center, Los Angeles, CA. They would like to thank Bojan Cercek, MD, PhD, for critically reviewing the manuscript, Kuang-Yuh Chyu, MD, for advice and suggestions, and Kamlesh Asotra, PhD, Adrian Glenn, Hao Zeng, MD, Ivan Velasquez, MD, and Susan Schaeaur, MS, for technical assistance.
PY - 2004
Y1 - 2004
N2 - Intracoronary brachytherapy (ICBT) effectively reduces restenosis but is associated with late thrombosis. Since tissue factor (TF) is an important mediator of arterial thrombosis, we tested the hypothesis that ICBT results in persistently augmented TF expression. Coronary arteries from 12 pigs were randomized to: control (C; no injury), oversized balloon injury (BI), or BI followed by ICBT. Animals were sacrificed at 1, 7, 14, or 60 days postprocedure, and coronary arteries collected for expression analyses and immunostaining. ICBT-treated arteries had higher TF antigen and activity at all time-points compared to BI arteries (Western blot: 16 571 ± 2090 vs 10 135 ± 2939 densitometric units, p = 0.001; ELISA: 0.42 ± 0.13 nM vs 0.25 ± 0.14 nM, p = 0.001; TF activity assay: 0.303 ± 0.11 nM vs 0.18 ± 0.07 nM, p = 0.01; immunohistochemical staining: 30.6 ± 6.6% vs 11.5% ± 3.2%, p = 0.01). TF expression increased following BI, increased further following ICBT, and persisted for the duration of the study. We conclude that TF expression increases after BI, but is further increased and persists for a longer duration following ICBT, suggesting that a TF-mediated mechanism may play a role in late thrombosis following ICBT.
AB - Intracoronary brachytherapy (ICBT) effectively reduces restenosis but is associated with late thrombosis. Since tissue factor (TF) is an important mediator of arterial thrombosis, we tested the hypothesis that ICBT results in persistently augmented TF expression. Coronary arteries from 12 pigs were randomized to: control (C; no injury), oversized balloon injury (BI), or BI followed by ICBT. Animals were sacrificed at 1, 7, 14, or 60 days postprocedure, and coronary arteries collected for expression analyses and immunostaining. ICBT-treated arteries had higher TF antigen and activity at all time-points compared to BI arteries (Western blot: 16 571 ± 2090 vs 10 135 ± 2939 densitometric units, p = 0.001; ELISA: 0.42 ± 0.13 nM vs 0.25 ± 0.14 nM, p = 0.001; TF activity assay: 0.303 ± 0.11 nM vs 0.18 ± 0.07 nM, p = 0.01; immunohistochemical staining: 30.6 ± 6.6% vs 11.5% ± 3.2%, p = 0.01). TF expression increased following BI, increased further following ICBT, and persisted for the duration of the study. We conclude that TF expression increases after BI, but is further increased and persists for a longer duration following ICBT, suggesting that a TF-mediated mechanism may play a role in late thrombosis following ICBT.
KW - Brachytherapy
KW - Porcine
KW - Restenosis
KW - Thrombosis
KW - Tissue factor
UR - http://www.scopus.com/inward/record.url?scp=12144289270&partnerID=8YFLogxK
U2 - 10.1080/14628840410030351
DO - 10.1080/14628840410030351
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C2 - 15204169
AN - SCOPUS:12144289270
SN - 1462-8848
VL - 6
SP - 20
EP - 27
JO - International Journal of Cardiovascular Interventions
JF - International Journal of Cardiovascular Interventions
IS - 1
ER -
