| First Author | Gelfand BD | Year | 2011 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 31 |
| Issue | 7 | Pages | 1625-33 |
| PubMed ID | 21527747 | Mgi Jnum | J:191469 |
| Mgi Id | MGI:5461793 | Doi | 10.1161/ATVBAHA.111.227827 |
| Citation | Gelfand BD, et al. (2011) Hemodynamic activation of beta-catenin and T-cell-specific transcription factor signaling in vascular endothelium regulates fibronectin expression. Arterioscler Thromb Vasc Biol 31(7):1625-33 |
| abstractText | OBJECTIVE: The goal of this study was to assess the activity of beta-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 beta-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 beta-catenin nuclear localization and fibronectin deposition. Exposure of endothelial cells to human-derived atheroprone shear stress induced nuclear localization of beta-catenin, transcriptional activation of TCF, and expression of fibronectin. Activation of fibronectin expression required beta-catenin, TCF, and the transcriptional coactivator CRBP-binding protein. Finally, we identified platelet endothelial cell adhesion molecule-1 as a critical regulator of constitutive beta-catenin and glycogen synthase kinase-3beta activities. CONCLUSIONS: These data reveal novel constitutive activation of the endothelial beta-catenin/TCF signaling pathway in atherosclerosis and regulation of fibronectin through hemodynamic shear stress. |
