Showing papers by "Jeffrey J. Rade published in 2009"
TL;DR: A novel mechanism of action of proteasome inhibitors is identified that may help to explain their clinically observed thromboprotective effects in patients at decreased risk for thromboembolic events.
Abstract: Objective— Impairment of the thrombomodulin–protein C anticoagulant pathway has been implicated in pathological thrombosis associated with malignancy. Patients who receive proteasome inhibitors as part of their chemotherapeutic regimen appear to be at decreased risk for thromboembolic events. We investigated the effects of proteasome inhibitors on endothelial thrombomodulin expression and function. Methods and Results— Proteasome inhibitors as a class markedly induced the expression of thrombomodulin and enhanced the protein C activating capacity of endothelial cells. Thrombomodulin upregulation was independent of NF-κB signaling, a principal target of proteasome inhibitors, but was instead a direct consequence of increased expression of the Kruppel-like transcription factors, KLF2 and KLF4. These effects were confirmed in vivo, where systemic administration of a proteasome inhibitor enhanced thrombomodulin expression that was paralleled by changes in the expression of KLF2 and KLF4. Conclusions— These findings identify a novel mechanism of action of proteasome inhibitors that may help to explain their clinically observed thromboprotective effects.
33 citations
TL;DR: It is shown that stretch-induced upregulation of COX-2 is mediated by activation of the NF-kappabeta signaling pathway.
26 citations
TL;DR: Induction of anti‐PF4/heparin antibodies, even those capable of heparin‐dependent platelet activation, is not independently associated with early saphenous vein graft occlusion or adverse clinical outcomes after CABG surgery.
25 citations
Patent•
01 Oct 2009
TL;DR: In this paper, a method for identifying an individual at elevated risk for vein graft occlusion after coronary artery or peripheral bypass graft surgery comprising conducting a thromboxane A2 generation analysis is presented.
Abstract: The present invention relates to methods, compositions, assays and kits are disclosed for identifying individuals with an elevated risk of experiencing an adverse cardiovascular event after coronary or peripheral arterial bypass graft surgery. In particular, the invention relates to a method for identifying an individual at elevated risk for vein graft occlusion after coronary artery or peripheral bypass graft surgery comprising conducting a thromboxane A2 generation analysis.
2 citations
Patent•
01 Oct 2009
TL;DR: In this article, a method for identifying an individual at elevated risk for vein graft occlusion after coronary artery or peripheral bypass graft surgery comprising conducting a platelet function analysis is presented.
Abstract: The present invention relates to methods, compositions, assays and kits for identifying individuals with elevated risk of experiencing an adverse cardiovascular event after coronary or peripheral arterial bypass graft surgery. In particular, the invention relates to a method for identifying an individual at elevated risk for vein graft occlusion after coronary artery or peripheral bypass graft surgery comprising conducting a platelet function analysis.