title: Lymphocyte populations in atherosclerotic lesions of apoE -/- and LDL receptor -/- mice. Decreasing density with disease progression.
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 microns2 x 10(3), 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.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Roselaar
authors.forename: P X
authors.initials: PX
authors.lastname: Kakkanathu
authors.forename: A
authors.initials: A
authors.lastname: Daugherty
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D018450:Disease Progression; D006937:Hypercholesterolemia / Q000097:blood / Q000235:genetics / Q000276:immunology*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D011973:Receptors, LDL; D002784:Cholesterol