Distribution of lipid deposits around aortic branches of mice lacking LDL receptors and apolipoprotein E.
Mice with inactivated genes are increasingly used as models of human atherosclerosis. The aim of the present study was to determine whether the characteristic age-related distributions of lipid deposition seen around human arterial branches are replicated in such mice. Lesions occur downstream of branch ostia in immature human aortas, but these regions are spared in adult vessels, with lesions occurring more frequently at the sides or upstream of the branches. We determined the pattern of lipid staining around 102 intercostal branch ostia from apolipoprotein E/low density lipoprotein receptor double-knockout mice aged 9 to 20 weeks by using en face microscopy and a frequency-mapping technique. Lesion prevalence was high in the ostium and the region immediately surrounding it. Frequencies were 2.12+/-0.30 (mean+/-SEM, n=11) times higher upstream than downstream (P<0.01), but the pattern did not resemble the adult human pattern: there were no peaks in frequency at the sides or upstream of the branch, and there was no sparing downstream. Furthermore, a patch of sparing upstream of the branch was seen, which has not been reported for human vessels, and there was no trend toward a more upstream pattern with age. We conclude that knockout mice may not be a suitable model in which to investigate localizing factors.
McGillicuddy
C J
CJ
School of Animal and Microbial Sciences, University of Reading, Reading, UK.
Carrier
M J
MJ
Weinberg
P D
PD
D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000473:pathology*; D004195:Disease Models, Animal; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics*
D001057:Apolipoproteins E; D008563:Membrane Lipids; D011973:Receptors, LDL