Paclitaxel induces up-regulation of tissue factor in human aortic endothelial cells

• Published in: International immunopharmacology Vol. 9; no. 1; pp. 144 - 147
• Main Authors: Wang, Huang-Joe, Huang, Haimei, Chuang, Yi-Ching, Huang, Huey-Chun
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 2009; Elsevier
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Aorta, Thoracic - cytology; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Biological and medical sciences; Blotting, Western; Cell Survival - drug effects; Cells, Cultured; Dose-Response Relationship, Drug; Drug-eluting stent; Drug-Eluting Stents; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism; Humans; In Vitro Techniques; Medical sciences; Paclitaxel; Paclitaxel - pharmacology; Pharmacology. Drug treatments; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Stent thrombosis; Tetrazolium Salts; Thiazoles; Thrombin - pharmacology; Thromboplastin - biosynthesis; Tissue factor; Up-Regulation - drug effects; Stent thrombosis; Endothelial cells; Drug-eluting stent; Paclitaxel; Tissue factor; Antineoplastic agent; Human; Endothelial cell; Cardiovascular disease; Thrombosis; Artery; Vascular disease; Taxane derivatives; Blood vessel; Aorta; Regulation; Circulatory system; Antimitotic; Drug eluting stent
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2008.10.003

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.