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Characterization of atherosclerotic lesions in apo E3-leiden transgenic mice.
Atherosclerosis. 1998 Jan; 136(1):147-52.A

Abstract

Apo E3-leiden transgenic mice express human dysfunctional apo E variant and develop hyperlipidemia and atherosclerosis on a high fat/high cholesterol diet. We characterized diet-induced atherosclerotic lesions in apo E3-leiden transgenic mice using immunocytochemical methods in order to examine foam cell formation and determine whether advanced atherosclerotic lesions develop in these animals. Special attention was given to the presence of oxidized lipoproteins and expression of lipoprotein receptors. Plasma cholesterol levels in apo E3-leiden mice on an atherogenic diet increased from 2 to 36 mmol/l in 4 months. At this time apo E3-leiden mice had developed lesions, which ranged from early fatty streaks in thoracic and abdominal aorta to advanced lesions in aortic arch. Early fatty streaks were entirely composed of macrophages which also expressed scavenger receptors. Epitopes characteristic of oxidized LDL were present in macrophage-rich foam cells. Advanced atherosclerotic lesions also developed in apo E3-leiden mice including smooth muscle cell cap formation and erosion of the media. Macrophages and epitopes characteristic of oxidized LDL were present in core and shoulder regions. Scavenger receptors were expressed in macrophages in advanced lesions, whereas LDL-receptor-related protein (LRP) was mainly expressed in smooth muscle cells. It is concluded that: (1) macrophages are the major cell type in both early and advanced atherosclerotic lesions; (2) scavenger receptors and oxidized lipoproteins are present in lesion macrophages; and (3) LRP is mostly expressed in smooth muscle cells. Thus, lesions in apo E3-leiden transgenic mice have features in common with human atherosclerosis. Since lesion macrophages also retain their ability to synthesize endogenous apo E, apo E3-leiden transgenic mouse may be a useful model for studies on the development and genetics of atherosclerosis.

Authors+Show Affiliations

A.I. Virtanen Institute, University of Kuopio, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9544741

Citation

Leppänen, P, et al. "Characterization of Atherosclerotic Lesions in Apo E3-leiden Transgenic Mice." Atherosclerosis, vol. 136, no. 1, 1998, pp. 147-52.
Leppänen P, Luoma JS, Hofker MH, et al. Characterization of atherosclerotic lesions in apo E3-leiden transgenic mice. Atherosclerosis. 1998;136(1):147-52.
Leppänen, P., Luoma, J. S., Hofker, M. H., Havekes, L. M., & Ylä-Herttuala, S. (1998). Characterization of atherosclerotic lesions in apo E3-leiden transgenic mice. Atherosclerosis, 136(1), 147-52.
Leppänen P, et al. Characterization of Atherosclerotic Lesions in Apo E3-leiden Transgenic Mice. Atherosclerosis. 1998;136(1):147-52. PubMed PMID: 9544741.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of atherosclerotic lesions in apo E3-leiden transgenic mice. AU - Leppänen,P, AU - Luoma,J S, AU - Hofker,M H, AU - Havekes,L M, AU - Ylä-Herttuala,S, PY - 1998/4/17/pubmed PY - 1998/4/17/medline PY - 1998/4/17/entrez SP - 147 EP - 52 JF - Atherosclerosis JO - Atherosclerosis VL - 136 IS - 1 N2 - Apo E3-leiden transgenic mice express human dysfunctional apo E variant and develop hyperlipidemia and atherosclerosis on a high fat/high cholesterol diet. We characterized diet-induced atherosclerotic lesions in apo E3-leiden transgenic mice using immunocytochemical methods in order to examine foam cell formation and determine whether advanced atherosclerotic lesions develop in these animals. Special attention was given to the presence of oxidized lipoproteins and expression of lipoprotein receptors. Plasma cholesterol levels in apo E3-leiden mice on an atherogenic diet increased from 2 to 36 mmol/l in 4 months. At this time apo E3-leiden mice had developed lesions, which ranged from early fatty streaks in thoracic and abdominal aorta to advanced lesions in aortic arch. Early fatty streaks were entirely composed of macrophages which also expressed scavenger receptors. Epitopes characteristic of oxidized LDL were present in macrophage-rich foam cells. Advanced atherosclerotic lesions also developed in apo E3-leiden mice including smooth muscle cell cap formation and erosion of the media. Macrophages and epitopes characteristic of oxidized LDL were present in core and shoulder regions. Scavenger receptors were expressed in macrophages in advanced lesions, whereas LDL-receptor-related protein (LRP) was mainly expressed in smooth muscle cells. It is concluded that: (1) macrophages are the major cell type in both early and advanced atherosclerotic lesions; (2) scavenger receptors and oxidized lipoproteins are present in lesion macrophages; and (3) LRP is mostly expressed in smooth muscle cells. Thus, lesions in apo E3-leiden transgenic mice have features in common with human atherosclerosis. Since lesion macrophages also retain their ability to synthesize endogenous apo E, apo E3-leiden transgenic mouse may be a useful model for studies on the development and genetics of atherosclerosis. SN - 0021-9150 UR - https://www.unboundmedicine.com/medline/citation/9544741/Characterization_of_atherosclerotic_lesions_in_apo_E3_leiden_transgenic_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9150(97)00196-2 DB - PRIME DP - Unbound Medicine ER -