Upregulation of tissue factor expression and thrombogenic activity in human aortic smooth muscle cells by irradiation, rapamycin and paclitaxel.
BACKGROUND
Intracoronary brachytherapy as well as rapamycin or paclitaxel coated stents reduce restenosis rates after stenting, but are associated with an increased risk of late stent thrombosis. Tissue factor (TF) may contribute to late thrombosis. This study examined the impact of rapamycin and paclitaxel on TF expression and compares the TF activity induction of both drugs and irradiation in SMCs.


METHODS
SMCs were stimulated with rapamycin, paclitaxel or irradiation. Real-time PCR, a chromogenic TF activity assay and Western blotting were done.


RESULTS
Rapamycin or paclitaxel increased the TF mRNA expression 5-fold and the TF activity 4- to 6-fold with a maximum at 5 h. Irradiation induced TF activity 2- to 4-fold with a maximum at 7 days.


CONCLUSIONS
The fast increase of TF expression in SMCs post rapamycin and paclitaxel treatment may explain acute stent thrombosis when anti-thrombotic therapies are withdrawn, whereas the irradiation induced long term increase of cellular thrombogenicity may contribute to late thrombosis post intracoronary brachytherapy. Therapies counteracting these side effects may reduce the risk of thrombotic complications after the coronary application of anti-proliferative therapies.
Eisenreich
Andreas
A
Charitè - Campus Benjamin Franklin -CharitéCentrum 11 für Herz-, Kreislauf- und Gefässmedizin, Berlin, Germany. andreas.eisenreich@charite.de <andreas.eisenreich@charite.de>
Celebi
Ozlem
O
Goldin-Lang
Petra
P
Schultheiss
Heinz-Peter
HP
Rauch
Ursula
U
D002478:Cells, Cultured; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D017239:Paclitaxel / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology*; D013925:Thromboplastin / Q000032:analysis / Q000235:genetics*; D013927:Thrombosis / Q000209:etiology*; D015854:Up-Regulation
D013925:Thromboplastin; D017239:Paclitaxel; D020123:Sirolimus