Bortezomib Improves Endothelial Thromboresistance Via Induction of KLF Transcription Factors

Background: Patients with multiple myeloma (MM) are at high risk for venothromboembolic events (VTE). Recent studies, however, suggest that MM patients treated with bortezomib, an approved proteasome inhibitor with potent NF-kB inhibitory effects, appear to have a lower risk of VTE compared to those...

Full description

Saved in:
Bibliographic Details
Published in:Blood 2008-11, Vol.112 (11), p.1890-1890
Main Authors: Hiroi, Toyoko, Deming, Clayton B, Zhao, Haige, Hansen, Baranda S, Arkenbout, Elisabeth K, Myers, Thomas J, Riordan, William J, McDevitt, Michael A, Rade, Jeffrey J
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background: Patients with multiple myeloma (MM) are at high risk for venothromboembolic events (VTE). Recent studies, however, suggest that MM patients treated with bortezomib, an approved proteasome inhibitor with potent NF-kB inhibitory effects, appear to have a lower risk of VTE compared to those treated with other therapies. We hypothesize that this could be due to a beneficial effect of bortezomib on endothelial thromboresistance. Methods and Results: Human umbilical vein endothelial cells (HUVECs) were incubated with bortezomib for 20 hours and changes in the expression of a panel of coagulation and inflammation-related genes measured by qPCR. Bortezomib stimulated baseline expression of anticoagulant genes (thrombomodulin (TM), eNOS and tissue factor pathway inhibitor), suppressed baseline expression of pro-coagulant genes (vWF and protease activated receptor-1) and suppressed cytokine-mediated induction of E-selectin, VCAM-1 and tissue factor. Most pronounced, was the dose-dependent upregulation of TM, a member of the protein C anticoagulant pathway (229 ± 15% and 341 ± 7% of control, at 5 nM and 10 nM bortezomib, respectively, p
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V112.11.1890.1890