Print Email Facebook Twitter Progression and regression of atherosclerosis in APOE3-Leiden transgenic mice: An immunohistochemical study 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 BiologyAtherosclerosisImmunohistochemistryProgressionRegressionTransgenic miceAnimalsAntibodies, MonoclonalAntigens, CD4AortaApolipoprotein E3Apolipoproteins EArteriosclerosisCell Adhesion MoleculesCholesterolCholesterol, DietaryDisease ProgressionEndothelium, VascularFemaleImmunohistochemistryIntercellular Adhesion Molecule-1MacrophagesMembrane GlycoproteinsMiceMice, TransgenicReceptors, ImmunologicReceptors, ScavengerT-LymphocytesTriglycerides To reference this document use: http://resolver.tudelft.nl/uuid:55efbdc4-1fcd-4b15-872b-df5df66bb083 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 Files To receive the publication files, please send an e-mail request to TNO Library.