Flow induced regulation of endothelial nitric oxide synthase (eNOS) gene expression: Role of shear sensitive promoter elements

Abstract

Vascular endothelium responds to hemodynamic forces such as shear stress by altering the synthesis and genetic expression of several proteins. Shear stress sensitive promoter elements and transcription factors may be involved in this signal transduction. Recently, two such promoter elements SSRE and TRE, have been identified. The eNOS gene promoter, has both SSRE and TRE, and thus can serve as a good model to study the role of these elements in shear stress signal transduction. Various 5$\sp\prime$-serial deletion mutants of a reporter gene vector containing the eNOS promoter, were transfected into cultured HUVECs, which were then subjected to well defined shear stresses using parallel plate flow chamber in a flow loop. Samples were withdrawn at different time points to quantitate NO release. Results suggest that shear stress induces NO release from endothelial cells in a dose dependent manner, and that the SSRE may be involved in the transcriptional upregulation of eNOS gene in response to arterial shear stress levels.