title: Identification of cholesterol crystals in plaques of atherosclerotic mice using hyperspectral CARS imaging.
abstract: The accumulation of lipids, including cholesterol, in the arterial wall plays a key role in the pathogenesis of atherosclerosis. Although several advances have been made in the detection and imaging of these lipid structures in plaque lesions, their morphology and composition have yet to be fully elucidated, particularly in different animal models of disease. To address this issue, we analyzed lipid morphology and composition in the atherosclerotic plaques of two animal models of disease, the low density lipoprotein receptor-deficient (LDLR(-/-)) mouse and the ApoE lipoprotein-deficient (ApoE(-/-)) mouse, utilizing hyperspectral coherent anti-Stokes Raman scattering (CARS) microscopy in combination with principal component analysis (PCA). Hyperspectral CARS imaging revealed lipid-rich macrophage cells and condensed needle-shaped and plate-shaped lipid crystal structures in both mice. Spectral analysis with PCA and comparison to spectra of pure cholesterol and cholesteryl ester derivatives further revealed these lipid structures to be pure cholesterol crystals, which were predominantly observed in the ApoE(-/-) mouse model. These results illustrate the ability of hyperspectral CARS imaging in combination with multivariate analysis to characterize atherosclerotic lipid morphology and composition with chemical specificity, and consequently, provide new insight into the formation of cholesterol crystal structures in atherosclerotic plaque lesions.
authors.affiliation: Department of Physiology and Biophysics, University of California, Irvine, CA; Laser Microbeam and Medical Program (LAMMP), University of California, Irvine, CA.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Lim
authors.affiliation: Laser Microbeam and Medical Program (LAMMP), University of California, Irvine, CA; Beckman Laser Institute, Department of Biomedical Engineering, University of California, Irvine, CA; Center for Complex Biological Systems, University of California, Irvine, CA and.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Suhalim
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Denver, CO.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Miyazaki-Anzai
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Denver, CO.
authors.forename: Makoto
authors.initials: M
authors.lastname: Miyazaki
authors.affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Denver, CO.
authors.forename: Moshe
authors.initials: M
authors.lastname: Levi
authors.affiliation: Laser Microbeam and Medical Program (LAMMP), University of California, Irvine, CA; Center for Complex Biological Systems, University of California, Irvine, CA and; Department of Chemistry, University of California, Irvine, CA; and.
authors.forename: Eric O
authors.initials: EO
authors.lastname: Potma
authors.affiliation: Laser Microbeam and Medical Program (LAMMP), University of California, Irvine, CA; Beckman Laser Institute, Department of Biomedical Engineering, University of California, Irvine, CA; Center for Complex Biological Systems, University of California, Irvine, CA and. Electronic address: bjtrombe@uci.edu.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Tromberg
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism; D002788:Cholesterol Esters / Q000737:chemistry / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology; D013059:Spectrum Analysis, Raman / Q000379:methods*; D014280:Triglycerides / Q000737:chemistry / Q000378:metabolism
chemical_list: D002788:Cholesterol Esters; D014280:Triglycerides; D002784:Cholesterol