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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1621.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Aortic Dissection Precedes Formation of Aneurysms and Atherosclerosis in Angiotensin II-Infused, Apolipoprotein E-Deficient Mice

Kiran Saraff; Fjoralba Babamusta; Lisa A. Cassis; Alan Daugherty

From the Division of Cardiovascular Medicine, Gill Heart Institute (K.S., F.B., A.D.), the Division of Pharmaceutical Science (L.A.C.), and the Department of Physiology (A.D.), University of Kentucky, Lexington.

Correspondence to Alan Daugherty, Center for Cardiovascular Research, Sanders Brown, Room 424, University of Kentucky, Lexington, KY 40536-0230. E-mail Alan.Daugherty{at}uky.edu

Objective— We sought to define the temporal characteristics of angiotensin II (AngII)-induced abdominal aortic aneurysms (AAAs) and to provide mechanistic insight into the development of this vascular pathology in apolipoprotein E-deficient (apoE-/-) mice.

Methods and Results— Male apoE-/- mice were infused with AngII for 1 to 56 days. Suprarenal arteries were sequentially sectioned, and cellular features were defined by histologic and immunocytochemical techniques. The initial identified event was medial accumulation of macrophages in regions of elastin degradation. Subsequent medial dissection was associated with luminal dilation and thrombus formation. Thrombi were usually constrained by adventitial tissue, although 10% of mice died due to rupture. Thrombi led to profound inflammation that was characterized by infiltration of macrophages and T and B lymphocytes. Remodeling of the tissues was associated with regeneration of elastin fibers and reendothelialization of the dilated luminal surface. Aneurysmal tissue underwent profound neovascularization. Atherosclerotic lesions were only detected after development of the aneurysms.

Conclusions— The initial event in AngII-induced AAA is a focal dissection in the suprarenal region. The progression of AAA precedes the development of overt atherosclerotic lesions.

Key Words: angiotensin • aneurysms • atherosclerosis

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