Deficiency of apolipoprotein E (APOE) causes familial dysbetalipoproteinemia in humans resulting in a higher risk of atherosclerotic disease. In mice, APOE deficiency results in a severe atherosclerosis phenotype, but it is unknown to what extent this is unique to mice. In this study, APOE was targeted in Yucatan minipigs. APOE−/− minipigs displayed increased plasma cholesterol and accumulation of apolipoprotein B-48–containing chylomicron remnants on low-fat diet, which was significantly accentuated upon feeding a high-fat, high-cholesterol diet. APOE−/− minipigs displayed accelerated progressive atherosclerosis but not xanthoma formation. This indicates that remnant lipoproteinemia does not induce early lesions but is atherogenic in pre-existing atherosclerosis.
Shim, J., Poulsen, C. B., Hagensen, M. K., Larsen, T., Heegaard, P. M. H., Christoffersen, C., … Sørensen, C. B. (2017). Apolipoprotein E Deficiency Increases Remnant Lipoproteins and Accelerates Progressive Atherosclerosis, But Not Xanthoma Formation, in Gene-Modified Minipigs. JACC: Basic to Translational Science, 2(5), 591–600. https://doi.org/10.1016/j.jacbts.2017.06.004