Title
Progression and regression of atherosclerosis in APOE3-Leiden transgenic mice: An immunohistochemical study
Author
Gijbels, M.J.J.
van der Cammen, M.
van der Laan, L.J.W.
Emeis, J.J.
Havekes, L.M.
Hofker, M.H.
Kraal, G.
Gaubius instituut TNO
Publication year
1999
Abstract
Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. We have studied the progression and regression of atherosclerosis using immunohistochemistry. Female transgenic mice were fed a moderate fat diet to study atherosclerosis over a longer time period. Fatty streaks arose in the intima and consisted of lipid filled macrophages which differed in origin. All macrophages expressed the macrophage scavenger receptor while two thirds expressed sialoadhesin and were positive for an antibody recognizing marginal zone macrophages (MOMA-1). All macrophages were negative for the scavenger receptor MARCO and 50% were positive for CD4. Small fatty streaks contained CD-3 positive T-lymphocytes which were for more than 70% CD4-positive. ICAM- 1 was positive both in atherosclerotic and control mice. In early plaques, fibrosis was observed on the luminal and medial site of the foam cells while smooth muscle cells were only observed in the fibrous cap. To study regression, we used a high fat, high cholesterol diet to rapidly induce atherosclerosis (14 weeks). The animals were then fed normal chow. Subsequently, atherosclerosis was assayed over time (4, 8, 16 weeks). Cholesterol levels dropped in 4 weeks to control levels. The animals did not show a significantly decrease in plaque size over time, but the percentage macrophages was significantly smaller in the animals after 4 weeks. In conclusion, the APOE3-Leiden mouse is a useful model to study the progression and regression of atherosclerosis.
Subject
Biology
Atherosclerosis
Immunohistochemistry
Progression
Regression
Transgenic mice
Animals
Antibodies, Monoclonal
Antigens, CD4
Aorta
Apolipoprotein E3
Apolipoproteins E
Arteriosclerosis
Cell Adhesion Molecules
Cholesterol
Cholesterol, Dietary
Disease Progression
Endothelium, Vascular
Female
Immunohistochemistry
Intercellular Adhesion Molecule-1
Macrophages
Membrane Glycoproteins
Mice
Mice, Transgenic
Receptors, Immunologic
Receptors, Scavenger
T-Lymphocytes
Triglycerides
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DOI
https://doi.org/10.1016/s0021-9150(98)00263-9
TNO identifier
234963
ISSN
0021-9150
Source
Atherosclerosis, 143 (1), 15-25
Document type
article