Multimodal CARS microscopy determination of the impact of diet on macrophage infiltration and lipid accumulation on plaque formation in ApoE-deficient mice[S]
We characterized several cellular and structural features of early stage Type II/III atherosclerotic plaques in an established model of atherosclerosis—the ApoE-deficient mouse—by using a multimodal, coregistered imaging system that integrates three nonlinear optical microscopy (NLOM) contrast mecha...
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| Format: | Article |
| Language: | English |
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Elsevier
2010-07-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520370954 |
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| author | Ryan S. Lim Adelheid Kratzer Nicholas P. Barry Shinobu Miyazaki-Anzai Makoto Miyazaki William W. Mantulin Moshe Levi Eric O. Potma Bruce J. Tromberg |
| author_facet | Ryan S. Lim Adelheid Kratzer Nicholas P. Barry Shinobu Miyazaki-Anzai Makoto Miyazaki William W. Mantulin Moshe Levi Eric O. Potma Bruce J. Tromberg |
| author_sort | Ryan S. Lim |
| collection | DOAJ |
| description | We characterized several cellular and structural features of early stage Type II/III atherosclerotic plaques in an established model of atherosclerosis—the ApoE-deficient mouse—by using a multimodal, coregistered imaging system that integrates three nonlinear optical microscopy (NLOM) contrast mechanisms: coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG), and two-photon excitation fluorescence (TPEF). Specifically, the infiltration of lipid-rich macrophages and the structural organization of collagen and elastin fibers were visualized by CARS, SHG, and TPEF, respectively, in thick tissue specimens without the use of exogenous labels or dyes. Label-free CARS imaging of macrophage accumulation was confirmed by histopathology using CD68 staining. A high-fat, high-cholesterol Western diet resulted in an approximate 2-fold increase in intimal plaque area, defined by CARS signals of lipid-rich macrophages. Additionally, analysis of collagen distribution within lipid-rich plaque regions revealed nearly a 4-fold decrease in the Western diet–fed mice, suggesting NLOM sensitivity to increased matrix metalloproteinase (MMP) activity and decreased smooth muscle cell (SMC) accumulation. These imaging results provide significant insight into the structure and composition of early stage Type II/III plaque during formation and allow for quantitative measurements of the impact of diet and other factors on critical plaque and arterial wall features. |
| first_indexed | 2024-12-18T01:39:49Z |
| format | Article |
| id | doaj.art-34dff783e53c463da93d61042bc70185 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-18T01:39:49Z |
| publishDate | 2010-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-34dff783e53c463da93d61042bc701852022-12-21T21:25:21ZengElsevierJournal of Lipid Research0022-22752010-07-0151717291737Multimodal CARS microscopy determination of the impact of diet on macrophage infiltration and lipid accumulation on plaque formation in ApoE-deficient mice[S]Ryan S. Lim0Adelheid Kratzer1Nicholas P. Barry2Shinobu Miyazaki-Anzai3Makoto Miyazaki4William W. Mantulin5Moshe Levi6Eric O. Potma7Bruce J. Tromberg8Laser Microbeam and Medical Program (LAMMP), Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA; Department of Physiology and Biophysics, University of California, Irvine, CADivision of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Denver, CODivision of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Denver, CODivision of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Denver, CODivision of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Denver, COLaser Microbeam and Medical Program (LAMMP), Beckman Laser Institute and Medical Clinic, University of California, Irvine, CADivision of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Denver, COLaser Microbeam and Medical Program (LAMMP), Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA; Department of Chemistry, University of California, Irvine, CATo whom correspondence should be addressed; Laser Microbeam and Medical Program (LAMMP), Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA; Department of Biomedical Engineering, University of California, Irvine, CAWe characterized several cellular and structural features of early stage Type II/III atherosclerotic plaques in an established model of atherosclerosis—the ApoE-deficient mouse—by using a multimodal, coregistered imaging system that integrates three nonlinear optical microscopy (NLOM) contrast mechanisms: coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG), and two-photon excitation fluorescence (TPEF). Specifically, the infiltration of lipid-rich macrophages and the structural organization of collagen and elastin fibers were visualized by CARS, SHG, and TPEF, respectively, in thick tissue specimens without the use of exogenous labels or dyes. Label-free CARS imaging of macrophage accumulation was confirmed by histopathology using CD68 staining. A high-fat, high-cholesterol Western diet resulted in an approximate 2-fold increase in intimal plaque area, defined by CARS signals of lipid-rich macrophages. Additionally, analysis of collagen distribution within lipid-rich plaque regions revealed nearly a 4-fold decrease in the Western diet–fed mice, suggesting NLOM sensitivity to increased matrix metalloproteinase (MMP) activity and decreased smooth muscle cell (SMC) accumulation. These imaging results provide significant insight into the structure and composition of early stage Type II/III plaque during formation and allow for quantitative measurements of the impact of diet and other factors on critical plaque and arterial wall features.http://www.sciencedirect.com/science/article/pii/S0022227520370954atherosclerosisextracellular matrixcollagenelastinarteriesnonlinear optical microscopy |
| spellingShingle | Ryan S. Lim Adelheid Kratzer Nicholas P. Barry Shinobu Miyazaki-Anzai Makoto Miyazaki William W. Mantulin Moshe Levi Eric O. Potma Bruce J. Tromberg Multimodal CARS microscopy determination of the impact of diet on macrophage infiltration and lipid accumulation on plaque formation in ApoE-deficient mice[S] Journal of Lipid Research atherosclerosis extracellular matrix collagen elastin arteries nonlinear optical microscopy |
| title | Multimodal CARS microscopy determination of the impact of diet on macrophage infiltration and lipid accumulation on plaque formation in ApoE-deficient mice[S] |
| title_full | Multimodal CARS microscopy determination of the impact of diet on macrophage infiltration and lipid accumulation on plaque formation in ApoE-deficient mice[S] |
| title_fullStr | Multimodal CARS microscopy determination of the impact of diet on macrophage infiltration and lipid accumulation on plaque formation in ApoE-deficient mice[S] |
| title_full_unstemmed | Multimodal CARS microscopy determination of the impact of diet on macrophage infiltration and lipid accumulation on plaque formation in ApoE-deficient mice[S] |
| title_short | Multimodal CARS microscopy determination of the impact of diet on macrophage infiltration and lipid accumulation on plaque formation in ApoE-deficient mice[S] |
| title_sort | multimodal cars microscopy determination of the impact of diet on macrophage infiltration and lipid accumulation on plaque formation in apoe deficient mice s |
| topic | atherosclerosis extracellular matrix collagen elastin arteries nonlinear optical microscopy |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520370954 |
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