Apolipoprotein E deficiency increases remnant lipoproteins and accelerates progressive atherosclerosis, but not xanthoma formation, in gene modified minipigs

Jeong Shim; Christian Bo Poulsen; Mette K. Hagensen; Torben Larsen; Peter Mikael Helweg Heegaard; Christina Christoffersen; Lars Bolund; Mette Schmidt; Ying Liu; Juan Li; Rong Li; Henrik Callesen; Jacob F. Bentzon; Charlotte B. Sørensen

doi:10.1016/j.jacbts.2017.06.004

Apolipoprotein E deficiency increases remnant lipoproteins and accelerates progressive atherosclerosis, but not xanthoma formation, in gene modified minipigs

Jeong Shim, Christian Bo Poulsen, Mette K. Hagensen, Torben Larsen, Peter Mikael Helweg Heegaard, Christina Christoffersen, Lars Bolund, Mette Schmidt, Ying Liu, Juan Li, Rong Li, Henrik Callesen, Jacob F. Bentzon, Charlotte B. Sørensen

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Abstract

Summary: 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.

Original language	English
Journal	J A C C: Basic to Translational Science
Volume	2
Issue number	5
Pages (from-to)	591-600
ISSN	2452-302X
DOIs	https://doi.org/10.1016/j.jacbts.2017.06.004
Publication status	Published - 2017

Bibliographical note

This is an open access article under the CC BY-NC-ND license.

Keywords

Apolipoprotein E
Atherosclerosis
Pig
Remnant cholesterol dysbetalipoproteinemia

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Shim, J., Poulsen, C. B., Hagensen, M. K., Larsen, T., Heegaard, P. M. H., Christoffersen, C., Bolund, L., Schmidt, M., Liu, Y., Li, J., Li, R., Callesen, H., Bentzon, J. F., & Sørensen, C. B. (2017). Apolipoprotein E deficiency increases remnant lipoproteins and accelerates progressive atherosclerosis, but not xanthoma formation, in gene modified minipigs. J A C C: Basic to Translational Science, 2(5), 591-600. https://doi.org/10.1016/j.jacbts.2017.06.004

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title = "Apolipoprotein E deficiency increases remnant lipoproteins and accelerates progressive atherosclerosis, but not xanthoma formation, in gene modified minipigs",

abstract = "Summary: 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.",

keywords = "Apolipoprotein E, Atherosclerosis, Pig, Remnant cholesterol dysbetalipoproteinemia",

author = "Jeong Shim and Poulsen, {Christian Bo} and Hagensen, {Mette K.} and Torben Larsen and Heegaard, {Peter Mikael Helweg} and Christina Christoffersen and Lars Bolund and Mette Schmidt and Ying Liu and Juan Li and Rong Li and Henrik Callesen and Bentzon, {Jacob F.} and S{\o}rensen, {Charlotte B.}",

note = "This is an open access article under the CC BY-NC-ND license.",

year = "2017",

doi = "10.1016/j.jacbts.2017.06.004",

language = "English",

volume = "2",

pages = "591--600",

journal = "J A C C: Basic to Translational Science",

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Shim, J, Poulsen, CB, Hagensen, MK, Larsen, T, Heegaard, PMH, Christoffersen, C, Bolund, L, Schmidt, M, Liu, Y, Li, J, Li, R, Callesen, H, Bentzon, JF & Sørensen, CB 2017, 'Apolipoprotein E deficiency increases remnant lipoproteins and accelerates progressive atherosclerosis, but not xanthoma formation, in gene modified minipigs', J A C C: Basic to Translational Science, vol. 2, no. 5, pp. 591-600. https://doi.org/10.1016/j.jacbts.2017.06.004

Apolipoprotein E deficiency increases remnant lipoproteins and accelerates progressive atherosclerosis, but not xanthoma formation, in gene modified minipigs. / Shim, Jeong; Poulsen, Christian Bo; Hagensen, Mette K. et al.
In: J A C C: Basic to Translational Science, Vol. 2, No. 5, 2017, p. 591-600.

Research output: Contribution to journal › Journal article › Research › peer-review

TY - JOUR

T1 - Apolipoprotein E deficiency increases remnant lipoproteins and accelerates progressive atherosclerosis, but not xanthoma formation, in gene modified minipigs

AU - Shim, Jeong

AU - Poulsen, Christian Bo

AU - Hagensen, Mette K.

AU - Larsen, Torben

AU - Heegaard, Peter Mikael Helweg

AU - Christoffersen, Christina

AU - Bolund, Lars

AU - Schmidt, Mette

AU - Liu, Ying

AU - Li, Juan

AU - Li, Rong

AU - Callesen, Henrik

AU - Bentzon, Jacob F.

AU - Sørensen, Charlotte B.

N1 - This is an open access article under the CC BY-NC-ND license.

PY - 2017

Y1 - 2017

N2 - Summary: 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.

AB - Summary: 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.

KW - Apolipoprotein E

KW - Atherosclerosis

KW - Pig

KW - Remnant cholesterol dysbetalipoproteinemia

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SN - 2452-302X

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SP - 591

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JO - J A C C: Basic to Translational Science

JF - J A C C: Basic to Translational Science

IS - 5

ER -

Apolipoprotein E deficiency increases remnant lipoproteins and accelerates progressive atherosclerosis, but not xanthoma formation, in gene modified minipigs

Abstract

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Keywords

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