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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:347.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Correlation of Vasa Vasorum Neovascularization and Plaque Progression in Aortas of Apolipoprotein E^–/–/Low-Density Lipoprotein^–/– Double Knockout Mice

Alexander C. Langheinrich; Agata Michniewicz; Daniel G. Sedding; Gerhard Walker; Patricia E. Beighley; Wigbert S. Rau; Rainer M. Bohle; Erik L. Ritman

From Mayo Clinic College of Medicine (A.C.L., P.E.B., E.L.R.), Rochester, Minn; Justus-Liebig University (A.C.L., A.M., D.G.S., G.W., W.S.R., R.M.B.), Giessen, Germany.

Correspondence to Erik L. Ritman, MD, PhD, Professor, Physiology and Medicine, Mayo Clinic College of Medicine, Alfred Bldg, 2-409, 200 First St SW, Rochester, MN 55905. E-mail elran{at}mayo.edu

Objective— We hypothesized that apolipoprotein E (apoE)^–/–/low-density lipoprotein (LDL)^–/– double knockout mice might develop vasa vasorum (VV) in association with advanced lesion formation.

Methods and Results— Aortas from apoE^–/–/LDL^–/– mice aged 16, 18, 20, or 80 weeks were infused in situ with Microfil, harvested, and scanned with micro-computed tomography (CT). We characterized plaque volume and CT "density" as well as VV luminal volume along the aorta using Analyze 6.0 software. Results were complemented by a detailed histological plaque classification according to American Heart Association guidelines. From 16 to 80 weeks, plaque volume and VV opacified lumen volume increased with age (P<0.001). The 3-dimensional micro-CT images of arterial and venous VV trees allowed perfusion territories to be delineated. The spatial location and magnitude of VV density and adventitial inflammation were strongly correlated in advanced atherosclerotic lesions (r=0.91) and identified as an independent correlate to advanced lesions. At age 80 weeks, VV luminal volume was increased 20-fold compared with animals at age 16 weeks (P<0.001). Micro-CT showed that adventitial VV communicate with intraplaque microvessels.

Conclusion— Our results show that apoE^–/–/LDL^–/– double knockout mice develop VV and advanced atheromas along the aorta. Lesion volume was closely associated with amount of neovascularization in advanced atheromas.

Lesion volume is closely associated with ectopic neovascularization in the aorta of apoE^–/–/LDL^–/– double knockout mice, suggesting that there may be a direct relationship between lesion growth and VV development.

Key Words: angiogenesis • atherosclerosisimaging • inflammation • micro-CT

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