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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1359.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Compensatory Enlargement and Stenosis Develop in ApoE^-/- and ApoE*3-Leiden Transgenic Mice

Esther Lutgens; Ebo D. de Muinck; Sylvia Heeneman; Mat J.A.P. Daemen

From the Departments of Pathology (E.L., S.H., M.J.A.P.D.) and Cardiology (E.D.d.M.), University of Maastricht, Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands.

Correspondence to M.J.A.P. Daemen, MD, PhD, Department of Pathology, P. Debeyelaan 25, PO Box 5800, 6202 AZ, Maastricht, Netherlands. E-mail MDA{at}LPAT.AZM.NL

Abstract—— Atherosclerotic mouse models develop little ischemic organ damage and no infarctions, despite the presence of large atherosclerotic lesions. Therefore, we hypothesize that luminal changes do not follow atherosclerotic lesion development. Because a phenomenon that may explain the discrepancy between luminal changes and lesion size is vascular remodeling, we measured parameters of vascular remodeling in the carotid arteries (CAs), thoracic aorta (TA), and abdominal aorta (AA) of apolipoprotein E (apoE)–deficient (apoE^-/-) and apoE*3-Leiden mice, 2 well-known mouse models of atherosclerosis. Atherosclerotic lesions were classified (American Heart Association [AHA] types II through V), and plaque thickness, compensatory enlargement versus constrictive remodeling, lumen diameter, stenosis, and media thickness were measured relative to the nondiseased arterial wall. In CAs, plaque thickness increased during atherogenesis. CAs showed compensatory enlargement (apoE^-/- 55%, apoE*3-Leiden 38%). Regression analysis revealed a positive correlation between plaque and lumen area (for apoE^-/-, R=0.95; for apoE*3-Leiden, R=0.90). Medial thinning and elastolysis were also observed. During atherogenesis, lumen diameter decreased (apoE^-/- -69%, apoE*3-Leiden -40%), and stenosis >70% developed. TA and AA showed similar features, but neither developed a progressive decrease in lumen diameter or stenosis >70%. In CAs, TA, and AA of apoE^-/- and apoE*3-Leiden mice, atherogenesis is associated with compensatory enlargement, medial thinning, and elastolysis. A progressive decrease in lumen diameter and stenoses >70% occur only in CAs. Vascular remodeling is more prominent in apoE^-/- mice.

Key Words: remodeling • animal models • atherosclerosis pathophysiology

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