To better understand a possible distinct role of ENaC-dependent mechanosensing in the regulation of endothelial function, we studied ENaC-dependent mechanisms under flow condition in in vitro microfluidic model mimicking laminar and non-laminar shear stress conditions as well as in vivo in control-wild-type mice and in ApoE/LDLR-/-mouse model for endothelial dysfunction and atherosclerosis. Here, APOE is linked to endothelial dysfunction.