- 作者：Bjö ; rn Szotowski ; Silvio Antoniak ; Petra Goldin-Lang ; Quoc-Viet Tran ; Klaus Pels ; Peter Rosenthal ; Vladimir Y. Bogdanov ; Hans-Hubert Borchert ; Heinz-Peter Schultheiss ; Ursula Rauch
- 关键词：Tissue factor ; Cytokines ; Apoptosis ; Antioxidants ; Pyrrolidine dithiocarbamate ; N-acetylcysteine
- 刊名：Cardiovascular Research
- 出版年：2007
- 期刊代码：48_00086363
- 类别：med
- 出版时间：1 March 2007
- 卷：73
- 期：4
- 页码：806-812
- 文件大小：543 K
The aim of this study was to investigate the effect of the antioxidants pyrrolidine dithiocarbamate (PDTC) and N-acetylcysteine (NAC) on the ionizing radiation (IR)- and tumor necrosis factor-α (TNF-α) induced tissue factor (TF) expression and its release from human umbilical vein endothelial cells (HUVECs).
Methods
HUVECs were irradiated with a single dose of either 5 Gy or 10 Gy and stimulated with TNF-α (10 ng/mL) in the presence or absence of PDTC and NAC, respectively. Quantitative real-time PCR, ELISA, and TF activity measurements were performed, including TF activity in the supernatant. Apoptosis was detected by flow cytometric active caspase-3 measurement and formation of reactive oxygen species (ROS) by chemiluminescence.
Results
We demonstrated a thus far uninvestigated persistent induction of TF expression in HUVECs after treatment with IR and TNF-α. Combined stimulation with IR and TNF-α led to an immense shedding of microparticle-associated TF which was positively correlated with apoptosis and ROS formation. Antioxidative pre-treatment reduced not only apoptosis and ROS formation, but also the release of thrombogenic microparticles.
Conclusions
Antioxidative treatment inhibited apoptosis and shedding of microparticles, thereby reducing thrombogenicity. Thus, antioxidants may help to prevent late thrombosis after antiproliferative treatment when used in combination with anticoagulants.