Characterization of Partial Ligation-Induced Carotid Atherosclerosis Model Using Dual-Modality Molecular Imaging in ApoE Knock-out Mice

Ik Jae Shin, Soo Min Shon, Dawid Schellingerhout, Jin Yong Park, Jeong Yeon Kim, Su Kyoung Lee, Dong Kun Lee, Ho Won Lee, Byeong Cheol Ahn, Kwang Meyung Kim, Ick Chan Kwon, Dong Eog Kim

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 (107 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.

Original languageEnglish
Article numbere73451
JournalPLoS One
Volume8
Issue number9
DOIs
Publication statusPublished - 2013 Sep 12
Externally publishedYes

Fingerprint

Molecular imaging
Carotid Artery Diseases
Molecular Imaging
carotid arteries
Common Carotid Artery
Arches
Apolipoproteins E
atherosclerosis
Knockout Mice
Ligation
Macrophages
Matrix Metalloproteinase 2
image analysis
Infrared radiation
Thoracic Aorta
Atherosclerosis
Matrix Metalloproteinase 9
mice
gelatinase A
Luciferases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Shin, I. J., Shon, S. M., Schellingerhout, D., Park, J. Y., Kim, J. Y., Lee, S. K., ... Kim, D. E. (2013). Characterization of Partial Ligation-Induced Carotid Atherosclerosis Model Using Dual-Modality Molecular Imaging in ApoE Knock-out Mice. PLoS One, 8(9), [e73451]. https://doi.org/10.1371/journal.pone.0073451

Characterization of Partial Ligation-Induced Carotid Atherosclerosis Model Using Dual-Modality Molecular Imaging in ApoE Knock-out Mice. / 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, Kwang Meyung; Kwon, Ick Chan; Kim, Dong Eog.

In: PLoS One, Vol. 8, No. 9, e73451, 12.09.2013.

Research output: Contribution to journalArticle

Shin, IJ, Shon, SM, Schellingerhout, D, Park, JY, Kim, JY, Lee, SK, Lee, DK, Lee, HW, Ahn, BC, Kim, KM, Kwon, IC & Kim, DE 2013, 'Characterization of Partial Ligation-Induced Carotid Atherosclerosis Model Using Dual-Modality Molecular Imaging in ApoE Knock-out Mice', PLoS One, vol. 8, no. 9, e73451. https://doi.org/10.1371/journal.pone.0073451
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, Kwang Meyung ; Kwon, Ick Chan ; Kim, Dong Eog. / Characterization of Partial Ligation-Induced Carotid Atherosclerosis Model Using Dual-Modality Molecular Imaging in ApoE Knock-out Mice. In: PLoS One. 2013 ; Vol. 8, No. 9.
@article{23df3a6a4c5140359d5c9fdad0968781,
title = "Characterization of Partial Ligation-Induced Carotid Atherosclerosis Model Using Dual-Modality Molecular Imaging in ApoE Knock-out Mice",
abstract = "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 (107 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.",
author = "Shin, {Ik Jae} and Shon, {Soo Min} and Dawid Schellingerhout and Park, {Jin Yong} and Kim, {Jeong Yeon} and Lee, {Su Kyoung} and Lee, {Dong Kun} and Lee, {Ho Won} and Ahn, {Byeong Cheol} and Kim, {Kwang Meyung} and Kwon, {Ick Chan} and Kim, {Dong Eog}",
year = "2013",
month = "9",
day = "12",
doi = "10.1371/journal.pone.0073451",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - Characterization of Partial Ligation-Induced Carotid Atherosclerosis Model Using Dual-Modality Molecular Imaging in ApoE Knock-out Mice

AU - Shin, Ik Jae

AU - Shon, Soo Min

AU - Schellingerhout, Dawid

AU - Park, Jin Yong

AU - Kim, Jeong Yeon

AU - Lee, Su Kyoung

AU - Lee, Dong Kun

AU - Lee, Ho Won

AU - Ahn, Byeong Cheol

AU - Kim, Kwang Meyung

AU - Kwon, Ick Chan

AU - Kim, Dong Eog

PY - 2013/9/12

Y1 - 2013/9/12

N2 - 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 (107 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.

AB - 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 (107 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.

UR - http://www.scopus.com/inward/record.url?scp=84884197940&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884197940&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0073451

DO - 10.1371/journal.pone.0073451

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e73451

ER -