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Updated: May 25, 2026

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Thioredoxin interacting protein promotes endothelial cell inflammation in response to disturbed flow by increasing
Xiao-Qun Wang1, Patrizia Nigro, Cameron World
1Aab Cardiovascular Research Institute, 601 Elmwood Avenue, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Rationale:
Endothelial cells (EC) at regions exposed to disturbed flow (d-flow) are predisposed to inflammation and the subsequent development of atherosclerosis. We previously showed that thioredoxin interacting protein (TXNIP) was required for tumor necrosis factor-mediated expression of vascular cell adhesion molecule-1.
Objective:
We sought to investigate the role of TXNIP in d-flow-induced cell adhesion molecule expression and leukocyte interaction with vessels, and the mechanisms by which TXNIP suppresses athero-protective gene expression.
Methods And Results:
Using en face staining of mouse aorta, we found a dramatic increase of TXNIP in EC at sites exposed to d-flow as compared to steady flow. EC-specific TXNIP (EC-TXNIP) knockout mice showed significant decreases in vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 mRNA expression in the d-flow regions of mouse aorta. Intravital microscopy of mesenteric venules showed that leukocyte rolling time was decreased, whereas rolling velocity was increased significantly in EC-TXNIP knockout mice. In vitro experiments using a cutout flow chamber to generate varying flow patterns showed that increased TXNIP was required for d-flow-induced EC-monocyte adhesion. Furthermore, we found that the expression of Kruppel-like factor 2, a key anti-inflammatory transcription factor in EC, was inhibited by TXNIP. Luciferase and chromatin immunoprecipitation assays showed that TXNIP was present within a repressing complex on the Kruppel-like factor 2 promoter.
Conclusions:
These data demonstrate the essential role for TXNIP in mediating EC-leukocyte adhesion under d-flow, as well as define a novel mechanism by which TXNIP acts as a transcriptional corepressor to regulate Kruppel-like factor 2-dependent gene expression.
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