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

Research output: Contribution to journalArticlepeer-review

353 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1621-1626
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume23
Issue number9
DOIs
StatePublished - Sep 1 2003

Keywords

  • Aneurysms
  • Angiotensin
  • Atherosclerosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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