Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:1013-1018
© 1996 American Heart Association, Inc.
Articles |
Lymphocyte Populations in Atherosclerotic Lesions of ApoE -/- and LDL Receptor -/- Mice
Decreasing Density With Disease Progression
the Departments of Medicine (S.E.R., P.X.K., A.D.) and Biochemistry and Molecular Biophysics (A.D.), Washington University School of Medicine, St Louis, Mo.
Correspondence to Alan Daugherty, Box 8086, Cardiovascular Division, Washington University School of Medicine, St Louis, MO 63110. E-mail doco@imgate.wustl.edu.
Abstract
Lymphocytes are prominent components of human atherosclerotic lesions, but their presence in murine models of disease has not been confirmed. Lymphocyte subpopulations have been identified in apoE -/- and LDL receptor -/- mice fed a cholesterol-enriched diet for up to 3 months. ApoE -/- mice had higher serum cholesterol concentrations than did LDL receptor -/- mice during most of the feeding period, primarily due to large increases in VLDL concentrations. Total area of atherosclerotic lesions was greater at all times in apoE -/- than LDL receptor -/- mice (lesion area after 3 months on cholesterol-enriched diet: apoE -/-, 993±193 and LDL receptor -/-, 560±131 µm2x103, mean±SEM, n=6 in each group). Lesions in apoE -/- mice contained larger macrophage-rich necrotic cores and more calcification than did those in LDL receptor -/- mice. Immunocytochemical analyses of tissue sections of ascending aortas performed with monoclonal antibodies to T and B lymphocytes and macrophages revealed that T lymphocytes immunoreactive for Thy 1.2, CD5, CD4, and CD8 were observed in lesions from both strains, but no B lymphocytes were detected. The density of Thy 1.2+ T lymphocytes in lesions was greatest at 1 month (apoE -/-, 98±23 and LDL receptor -/-, 201±40 lymphocytes/mm2, n=6 in each group), decreasing in apoE -/- mice to 12±3 and in LDL receptor -/- mice to 51±20 lymphocytes/mm2 at 3 months. The presence of T lymphocytes in murine atherosclerotic lesions makes these animals potentially useful for studying the involvement of the immune system in atherogenesis.
Key Words: atherosclerosis • murine model • T lymphocytes • immunohistochemistry
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