Endothelium-derived nitric oxide (NO) is a critical regulator of cardiovascular homeostasis. Endothelial nitric oxide synthase (eNOS or NOS3)-derived NO is an endogenous vasodilatory gas that continually regulates the diameter of blood vessels and maintains an anti-proliferative and anti-apoptotic environment in the vessel wall. Initially thought to be a simple, calmodulin (CaM) regulated enzyme, it is clear that eNOS has evolved to be tightly controlled by co- and post-translational lipid modifications, phosphorylation on multiple residues and regulated protein-protein interactions (Fulton et al., 2001).FIG1
Physiologically, endothelial cells are exposed to the hemodynamic forces of blood including laminar shear stress. Shear stress, via G proteins (Gs), can activate several signal transduction pathways, including the phosphoinoside 3-kinase (PI3K) and adenylate cyclase (AC) pathways, leading to eNOS activation via phosphorylation of serine residues (S617 and S1179 for Akt, and S635 and S1179 for PKA), which promote eNOS activation. Shear stress also increases...
