When present elsewhere in the arterial circulation, e.g., at bifurcations, the inner arch of the aorta or downstream of plaques, low and disturbed shear stress favors a non-aligned cobblestoned EC morphology that is associated with increased oxidative stress, inflammation, markers of aging, and low eNOS/NO activity (i.e., endothelial dysfunction) [28,29,30,31,44,45]. Here, NOS3 is linked to endothelial dysfunction.