Shin, Ik Jae Shon, Soo-Min Schellingerhout, Dawid Park, Jin-Yong Kim, Jeong-Yeon Lee, Su Kyoung Lee, Dong Kun Lee, Ho Won Ahn, Byeong-Cheol Kim, Kwangmeyung Kwon, Ick Chan Kim, Dong-Eog 2024-01-20T11:32:43Z 2024-01-20T11:32:43Z 2021-09-04 2013-09-12 1932-6203 https://pubs.kist.re.kr/handle/201004/127668 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. Methodology and Principal Findings: 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/Significance: 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. English PUBLIC LIBRARY SCIENCE MATRIX METALLOPROTEINASES INCREASED EXPRESSION HEME OXYGENASE-1 IN-VIVO MOUSE FLOW ARTERY ATHEROGENESIS INFLAMMATION TARGET Characterization of Partial Ligation-Induced Carotid Atherosclerosis Model Using Dual-Modality Molecular Imaging in ApoE Knock-out Mice Article 10.1371/journal.pone.0073451 1 PLOS ONE, v.8, no.9 PLOS ONE 8 9 scie scopus 000326240100044 2-s2.0-84884197940 Multidisciplinary Sciences Science & Technology - Other Topics Article MATRIX METALLOPROTEINASES INCREASED EXPRESSION HEME OXYGENASE-1 IN-VIVO MOUSE FLOW ARTERY ATHEROGENESIS INFLAMMATION TARGET