Shear stress gene expression regulated

NOS III is found to be constitutively expressed in endothelial cells and some other cell types (see below). Some mechanisms that also regulate the expression of the NOS III gene have been described. Shear stress produced by the flowing blood not only increases endothelial NO release acutely (Lamontagne etal., 1992) but also up-regulates NOS III expression (Nishida et al., 1992). A putative shear stress-responsive element has been described... 

In turn, MAPKs are also involved in the regulation of the gene expression of all three NOS isoenzymes. The expression of iNOS (NOS-2) is regulated by all three MAP kinase pathways in a variety of cell types [125-129]. For example, INK and ERKl/2 pathways are necessary for lipopolysaccharide (LPS-) and interferon-y-stimulated iNOS expression in mouse macrophage cells, possibly via a-tumor necrosis factor secretion, whereas p38 inhibited induction [130]. The induction of endothelial NOS (eNOS, NOS-3) by estrogen, fibroblast growth factor, or epidermal growth factor in endothelial cells involves the Ras-ERK pathway [131,132]. eNOS is phosphorylated, and thus activated, by the serine/threonine protein kinase Akt, which is recruited to the cell membrane by PI3-kinase as an antiapoptotic mechanism in the response of endothelial cells to shear stress [133]. 

The discovery of the role of NO in circulatory regulation introduced awareness that blood imparts shear stress to the endothelial cells lining blood vessels. These hemodynamic forces induce various functional stimuli to the vascular endothelium leading to the production of NO and alterations in a variety of functionally important factors, many of which are regulated by gene expression [24,95]. In this context, the role of blood viscosity and how this is affected by potential blood substitutes is becoming increasingly important. 

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