Thioredoxin interacting protein promotes endothelial cell inflammation in response to disturbed flow by increasing leukocyte adhesion and repressing Kruppel-like factor 2.

Cellular Biology Thioredoxin Interacting Protein Promotes Endothelial Cell Inflammation in Response to Disturbed Flow by Increasing Leukocyte Adhesion and Repressing Kruppel-Like Factor 2

Novel mechanisms of endothelial mechanotransduction.

Atherosclerosis is a focal disease that develops preferentially where nonlaminar, disturbed blood flow occurs, such as branches, bifurcations, and curvatures of large arteries. Endothelial cells sense and respond differently to disturbed flow compared with steady laminar flow. Disturbed flow that occurs in so-called atheroprone areas activates proinflammatory and apoptotic signaling, and this r...

Thioredoxin-interacting protein mediates TRX1 translocation to the plasma membrane in response to tumor necrosis factor-α: a key mechanism for vascular endothelial growth factor receptor-2 transactivation by reactive oxygen species.

OBJECTIVE Thioredoxin-interacting protein (TXNIP) promotes inflammation in endothelial cells (EC) by binding to thioredoxin-1 (TRX1) in a redox-dependent manner. Formation of the TXNIP-TRX1 complex relieves inhibition of the apoptosis signal-regulating kinase 1-c-Jun N-terminal kinase-vascular cell adhesion molecule-1 pathway. Because TXNIP is an α-arrestin with numerous protein-protein interac...

Disturbed Flow Enhances Inflammatory Signaling and Atherogenesis by Increasing Thioredoxin-1 Level in Endothelial Cell Nuclei

BACKGROUND Oxidative stress occurs with disturbed blood flow, inflammation and cardiovascular disease (CVD), yet free-radical scavenging antioxidants have shown limited benefit in human CVD. Thioredoxin-1 (Trx1) is a thiol antioxidant protecting against non-radical oxidants by controlling protein thiol/disulfide status; Trx1 translocates from cytoplasm to cell nuclei due to stress signaling, fa...

Thioredoxin-interacting protein is a biomechanical regulator of Src activity: key role in endothelial cell stress fiber formation.

RATIONALE Fluid shear stress differentially regulates endothelial cell stress fiber formation with decreased stress fibers in areas of disturbed flow compared with steady flow areas. Importantly, stress fibers are critical for several endothelial cell functions including cell shape, mechano-signal transduction, and endothelial cell-cell junction integrity. A key mediator of steady flow-induced ...