Paclitaxel induces up-regulation of tissue factor in human aortic endothelial cells.
Patients who underwent paclitaxel-eluting stent implantation are at a risk of developing late stent thrombosis. However, it is unclear whether paclitaxel alone can modulate tissue factor (TF) expression in human aortic endothelial cells (HAEC). HAEC were stimulated with paclitaxel. Western blotting, real-time PCR, and a chromogenic TF activity assay were done. In HAEC, while paclitaxel (10 (-5) mol/L to 10 (-9) mol/L) treatment for 5 h up-regulated the expression of TF in a dose-dependent manner, paclitaxel cotreatment with thrombin further enhanced it. While paclitaxel (10 (-5) mol/L) itself induced a 3.7-fold enhancement in TF activity, its cotreatment along with thrombin elicited a 7.6-fold increase in TF activity. Paclitaxel also caused an 8.1-fold increase in TF mRNA expression, and paclitaxel cotreatment with thrombin caused a 13.6-fold enhancement in TF mRNA expression. In summary, paclitaxel alone can up-regulate endothelial TF expression. These findings are significant for the patients receiving paclitaxel-eluting stents, and they may provide opportunities to develop novel therapeutic strategies for DES thrombosis.
Wang
Huang-Joe
HJ
Division of Cardiology, Department of Medicine, China Medical University Hospital, Taiwan; Institute of Biotechnology, National Tsing Hua University, Taiwan.
Huang
Haimei
H
Chuang
Yi-Ching
YC
Huang
Huey-Chun
HC
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D017239:Paclitaxel / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D013917:Thrombin / Q000494:pharmacology; D013925:Thromboplastin / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D013925:Thromboplastin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D013917:Thrombin; C022616:thiazolyl blue; D017239:Paclitaxel