JACC: Basic to Translational Science (Oct 2017)

Apolipoprotein E Deficiency Increases Remnant Lipoproteins and Accelerates Progressive Atherosclerosis, But Not Xanthoma Formation, in Gene-Modified Minipigs

  • Jeong Shim, MD,
  • Christian Bo Poulsen, MD, PhD,
  • Mette K. Hagensen, MSc, PhD,
  • Torben Larsen, MSc, PhD,
  • Peter M.H. Heegaard, MSc, PhD,
  • Christina Christoffersen, MD, PhD, DMSc,
  • Lars Bolund, MD, DMSc,
  • Mette Schmidt, DVM, PhD,
  • Ying Liu, MSc, PhD,
  • Juan Li, MSc, PhD,
  • Rong Li, MSc, PhD,
  • Henrik Callesen, DVM, PhD, DrVetSci,
  • Jacob F. Bentzon, MD, PhD,
  • Charlotte B. Sørensen, MSc, PhD

DOI
https://doi.org/10.1016/j.jacbts.2017.06.004
Journal volume & issue
Vol. 2, no. 5
pp. 591 – 600

Abstract

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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.

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