Combined, these data provide evidence that endothelial NOTCH1 signaling correlates positively with the level of shear stress in the aorta in vivo and that the presence of Notch1 in the descending aorta protects the endothelium from atherosclerotic plaque build-up in the advent of hypercholesterolemia. The gene discussed is NOTCH1; the disease is familial hypercholesterolemia.