As endothelial dysfunction typically precedes the development and progression of atherosclerosis, we speculate that the observed improvement of endothelial function in Apoe−/− HFD mice by SKA-31 treatment may oppose the functional impairments of CV performance that develop beyond the early stage of atherosclerosis when plaques become more permanent and progressive, rather than directly reduce plaque formation. Here, APOE is linked to endothelial dysfunction.