Published in:
FEBS Letters, 535 (2003) 1-3, Seite 87-93
Language:
English
DOI:
10.1016/s0014-5793(02)03879-6
ISSN:
0014-5793;
1873-3468
Origination:
Footnote:
Description:
Hemodynamic forces play a fundamental role in the regulation of endothelial cell survival. As signaling via the vascular endothelial growth factor (VEGF) receptor‐2 pathway has been previously demonstrated to impact endothelial cell survival, we hypothesized that laminar shear stress may facilitate survival in part by inducing VEGF receptor‐2 expression. This study shows a time‐ and dose‐dependent upregulation of endothelial VEGF receptor‐2 expression by fluid shear stress in microvascular and large‐vessel derived endothelial cells. A functional analysis of the 5′‐regulatory region of the VEGF receptor‐2 promoter localized the shear stress‐response element to a sequence between bp −60 and −37 that encompasses two adjacent consensus Sp1 transcription factor binding sites. Constitutive and shear stress‐inducible Sp1‐dependent complexes are bound to this element, indicating that fluid shear stress‐induced transcriptional activation of the VEGF receptor‐2 gene requires Sp1‐dependent DNA binding. Together, these results suggest that biomechanical stimulation may lead to endothelial cell survival by upregulating VEGF receptor‐2 expression.