Proteasome inhibitors enhance endothelial thrombomodulin expression via induction of Kruppel-like transcription factors.

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-kappaB signaling, a principal target of proteasome inhibitors, but was instead a direct consequence of increased expression of the Krüppel-like transcription fact

SUBMITTER: Hiroi T 

PROVIDER: S-EPMC2752639 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature