Characterization of partial ligation-induced carotid atherosclerosis model using dual-modality molecular imaging in ApoE knock-out mice.
BACKGROUND
Recently, partial ligation of the common carotid artery (CCA) was reported to induce carotid atheromata rapidly in apolipoprotein-E knockout (ApoE(-/-)) mice. We investigated this new atherosclerosis model by using combined matrix-metalloproteinase (MMP) near-infrared fluorescent (NIRF) imaging and macrophage-tracking luciferase imaging.


RESULTS
Partial ligation of the left CCA was performed in 10-week-old ApoE(-/-) mice on a high fat diet (n=33); the internal and external carotid arteries and occipital artery were ligated, while the superior thyroid artery was left intact. Two thirds of the animals were treated with either LiCl or atorvastatin. At 1-week, Raw264.7 macrophages modified to express the enhanced firefly-luciferase reporter gene (10(7) Raw-luc cells) were injected intravenously. At 2-week, NIRF molecular imaging visualized strong MMP-2/9 activity in the ligated area of the left CCA as well as in the aortic arch. Left-to-right ratios of the NIRF signal intensities in the CCA had a decreasing gradient from the highest value in the upper-most ligated area to the lowest value in the lower-most region adjacent to the aortic arch. Luciferase imaging showed that most Raw-luc macrophages were recruited to the ligated area of the CCA rather than to the aortic arch, despite similarly strong MMP-2/9-related NIRF signal intensities in both areas. In addition, LiCl or atorvastatin could reduce MMP-2/9 activity in the aortic arch but not in the ligated area of the CCA.


CONCLUSIONS
This is the first molecular imaging study to characterize the partial ligation-induced carotid atherosclerosis model. Molecularly divergent types of atherosclerosis were identified: conventional lipogenic atherosclerosis in the aorta vs. flow-related mechanical atherosclerosis in the partially ligated left system.
Molecular Imaging and Neurovascular Research (MINER) Laboratory, Dongguk University College of Medicine, Goyang, Korea.
Ik Jae
IJ
Shin
Soo-Min
SM
Shon
Dawid
D
Schellingerhout
Jin-Yong
JY
Park
Jeong-Yeon
JY
Kim
Su Kyoung
SK
Lee
Dong Kun
DK
Lee
Ho Won
HW
Lee
Byeong-Cheol
BC
Ahn
Kwangmeyung
K
Kim
Ick Chan
IC
Kwon
Dong-Eog
DE
Kim
D000818:Animals; D001057:Apolipoproteins E; D000069059:Atorvastatin; D002340:Carotid Artery Diseases / Q000209:etiology / Q000473:pathology*; D002460:Cell Line; D006538:Heptanoic Acids / Q000494:pharmacology; D008026:Ligation / Q000009:adverse effects; D018021:Lithium Chloride; D051379:Mice; D018345:Mice, Knockout; D057054:Molecular Imaging / Q000379:methods*; D011758:Pyrroles / Q000494:pharmacology
D001057:Apolipoproteins E; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D018021:Lithium Chloride