Uremic Serum and Ubiquitylation of Tissue Factor

Stent thrombosis is a major clinical problem associated with a high rate of mortality.1,2 The development of drug-eluting stents has significantly reduced restenosis compared with bare metal stents as a result of the antiproliferative agents inhibiting vascular smooth muscle (VSMC) proliferation. However, the rate of stent thrombosis associated with drug-eluting stents continues to be a major concern, with rates between 0.3 and 1.1% within 3 years.1 Thrombosis is likely in part attributable to the fact that the antiproliferative drugs also inhibit re-endothelization of the vessel. Furthermore, patients with chronic renal failure have worse outcomes after stenting and have as much as an 8-fold increase in 1-year cardiac mortality after coronary intervention.3Article see p 365 Tissue factor (TF) is a transmembrane protein that triggers blood coagulation.4 It has been proposed that TF plays a role in stent thrombosis, although there is no direct evidence for this assumption in patients. Platelet binding to the damaged vessel with or without exposure of TF is equally likely to trigger thrombosis. In this issue of Circulation , Chitalia et al5 have made the interesting observation that uremic serum increases TF protein stability in VSMCs. They suggest that this may explain the increase in cardiac mortality in chronic renal failure patients receiving stents.In healthy vessels, TF is separated from its ligand factor VII/VIIa in the blood by the endothelium, and this prevents inadvertent activation of …