Progression and regression of atherosclerosis in APOE3-Leiden transgenic mice: an immunohistochemical study

Apolipoprotein E3-Leiden (APOE3-Leiden) transgenic mice develop hyperlipide mia and are highly susceptible to diet-induced atherosclerosis. We have stu died the progression and regression of atherosclerosis using immunohistoche mistry. Female transgenic mice were fed a moderate fat diet to study athero sclerosis over a longer time period. Fatty streaks arose in the intima and consisted of lipid filled macrophages which differed in origin. All macroph ages expressed the macrophage scavenger receptor while two thirds expressed sialoadhesin and were positive for an antibody recognizing marginal zone m acrophages (MOMA-1). All macrophages were negative for the scavenger recept or 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 wa s positive both in atherosclerotic and control mice. In early plaques, fibr osis was observed on the luminal and medial site of the foam cells while sm ooth muscle cells were only observed in the fibrous cap. To study regressio n, we used a high fat, high cholesterol diet to rapidly induce atherosclero sis (14 weeks). The animals were then fed normal chow. Subsequently, athero sclerosis was assayed over time (4, 8, 16 weeks). Cholesterol levels droppe d in 4 weeks to control levels. The animals did not show a significantly de crease in plaque size over time, but the percentage macrophages was signifi cantly smaller in the animals after 4 weeks. In conclusion, the APOE3-Leide n mouse is a useful model to study the progression and regression of athero sclerosis. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.