Hemodynamic activation of β-catenin and T-cell-specific transcription factor signaling in vascular endothelium regulates fibronectin expression
BD Gelfand, J Meller, AW Pryor, M Kahn… - … , and vascular biology, 2011 - Am Heart Assoc
BD Gelfand, J Meller, AW Pryor, M Kahn, PDS Bortz, BR Wamhoff, BR Blackman
Arteriosclerosis, thrombosis, and vascular biology, 2011•Am Heart AssocObjective—The goal of this study was to assess the activity of β-catenin/T-cell-specific
transcription factor (TCF) signaling in atherosclerosis development and its regulation of
fibronectin in vascular endothelium. Methods and Results—Histological staining identified
preferential nuclear localization of β-catenin in the endothelium of atheroprone aorta before
and during lesion development. Transgenic reporter studies revealed that increased levels
of TCF transcriptional activity in endothelium correlated anatomically with β-catenin nuclear …
transcription factor (TCF) signaling in atherosclerosis development and its regulation of
fibronectin in vascular endothelium. Methods and Results—Histological staining identified
preferential nuclear localization of β-catenin in the endothelium of atheroprone aorta before
and during lesion development. Transgenic reporter studies revealed that increased levels
of TCF transcriptional activity in endothelium correlated anatomically with β-catenin nuclear …
Objective
The goal of this study was to assess the activity of β-catenin/T-cell-specific transcription factor (TCF) signaling in atherosclerosis development and its regulation of fibronectin in vascular endothelium.
Methods and Results
Histological staining identified preferential nuclear localization of β-catenin in the endothelium of atheroprone aorta before and during lesion development. Transgenic reporter studies revealed that increased levels of TCF transcriptional activity in endothelium correlated anatomically with β-catenin nuclear localization and fibronectin deposition. Exposure of endothelial cells to human-derived atheroprone shear stress induced nuclear localization of β-catenin, transcriptional activation of TCF, and expression of fibronectin. Activation of fibronectin expression required β-catenin, TCF, and the transcriptional coactivator CRBP-binding protein. Finally, we identified platelet endothelial cell adhesion molecule-1 as a critical regulator of constitutive β-catenin and glycogen synthase kinase-3β activities.
Conclusion
These data reveal novel constitutive activation of the endothelial β-catenin/TCF signaling pathway in atherosclerosis and regulation of fibronectin through hemodynamic shear stress.
Am Heart Assoc