Intracoronary beta-irradiation enhances balloon-injury-induced tissue factor expression in the porcine injury model.
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.
Finkelstein
Ariel
A
The Cardiovascular Intervention Research Center, Cedars-Sinai Medical Center and David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Hausleiter
Joerg
J
Doherty
Terence
T
Takizawa
Kaname
K
Bergman
Jonathan
J
Liu
Ming
M
Rukshin
Vladimir
V
Fishbein
Michael
M
Eigler
Neal
N
Shah
Prediman
P
Rajavashisth
Tripathi
T
Makkar
Raj
R
D000818:Animals; D015153:Blotting, Western; D001918:Brachytherapy / Q000379:methods*; D002404:Catheterization / Q000009:adverse effects*; D023903:Coronary Restenosis / Q000209:etiology; D003328:Coronary Thrombosis / Q000209:etiology; D003331:Coronary Vessels / Q000293:injuries* / Q000528:radiation effects*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D013552:Swine; D013925:Thromboplastin / Q000378:metabolism*
D013925:Thromboplastin