Correlation of vasa vasorum neovascularization and plaque progression in aortas of apolipoprotein E(-/-)/low-density lipoprotein(-/-) double knockout mice.
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.


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.


CONCLUSIONS
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.
Langheinrich
Alexander C
AC
Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Michniewicz
Agata
A
Sedding
Daniel G
DG
Walker
Gerhard
G
Beighley
Patricia E
PE
Rau
Wigbert S
WS
Bohle
Rainer M
RM
Ritman
Erik L
EL
D000818:Animals; D001011:Aorta / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D008077:Lipoproteins, LDL / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology*; D014651:Vasa Vasorum / Q000473:pathology*; D014657:Vasculitis / Q000235:genetics / Q000473:pathology
D001057:Apolipoproteins E; D008077:Lipoproteins, LDL