The main findings of this study are: (i) Cav-1 is essential for oxLDL-induced endothelial stiffening via regulation of oxLDL uptake in vitro and for high fat diet-induced hypercholesterolemia in vivo; (ii) Cav-1 plays a major role in endothelial stiffening observed in cells exposed to pro-atherogenic disturbed flow in the presence of oxLDL, which corresponds to endothelial stiffening in the atheroprone region of the aortic arch and finally (iii) Cav-1 plays a significant role in endothelial stiffening in ageing aortas. Here, CAV1 is linked to Hypercholesterolemia.