doi: 10.1161/hq0302.105378
© 2002 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Accumulation of Biglycan and Perlecan, but Not Versican, in Lesions of Murine Models of Atherosclerosis
From Massachusetts General Hospital and Harvard (V.V.K.), Boston, Mass, and the Department of Medicine (D.S.C., K.D.O., R.C.L.) and Departments of Pathobiology and Nutritional Sciences (R.C.L.), University of Washington, Seattle.
Reprint requests to Dr Renée C. LeBoeuf, Department of Pathobiology, Box 353410, Room 305, Raitt Hall, University of Washington, Seattle, WA 98195-3140. E-mail leboeuf{at}u.washington.edu
Proteoglycan accumulation within the arterial intima has been implicated in lipoprotein retention and in atherosclerosis progression in humans. Two commonly studied murine models of atherosclerosis, the apolipoprotein E (apoE)-deficient (apoE-/-) mouse and the low density lipoprotein receptor–deficient (LDLR-/-) mouse, develop arterial lesions similar to those of human atherosclerosis. However, specific proteoglycan classes that accumulate in lesions of these mice and their relation to the retention of specific apolipoproteins have not been previously determined. In this report, we characterized the distribution of proteoglycans (versican, biglycan, and perlecan) and apolipoproteins (apoB, apoA-I, and apoE) in proximal aortic lesions of chow-fed apoE-/- and LDLR-/- mice at 10, 52, and 73 weeks of age. We observed that similar to the apoE-/- mice, the LDLR-/- mice develop intermediate and advanced plaques within 52 weeks of age. Perlecan and biglycan (both are proteoglycans) appeared early in lesion development with distinct expression patterns as the plaques advanced. Versican, a major proteoglycan detected in human plaques, was mostly absent in both strains. ApoA-I and apoB were detected in early through advanced lesions in regions of proteoglycan accumulation in both strains. Our results indicate that proteoglycans may contribute to the retention of lipoproteins at the earliest stage of atherosclerosis in murine models of atherosclerosis.
Key Words: apoE deficiency • LDL receptor deficiency • atherosclerosis • proteoglycans • apolipoproteins
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