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Lipid crystals mechanically stimulate adjacent extracellular matrix in advanced atherosclerotic plaques

Title
Lipid crystals mechanically stimulate adjacent extracellular matrix in advanced atherosclerotic plaques
Authors
Lee, ES[Lee, Eun-Soo]Park, JH[Park, Joo Hyun]Lee, SW[Lee, Sang-Won]Hahn, J[Hahn, Junhee]Lee, H[Lee, Haea]Chae, SW[Chae, Soo-Won]Lee, TG[Lee, Tae Geol]Moon, DW[Moon, Dae Won]Kim, SH[Kim, Se-Hwa]
DGIST Authors
Moon, DW[Moon, Dae Won]
Issue Date
2014-12
Citation
Atherosclerosis, 237(2), 769-776
Type
Article
Article Type
Article
Keywords
AdventitiaAnimal TissueArteryAtherosclerotic PlaqueCollagenComparative StudyConfocal Laser MicroscopyControlled StudyCrystalDescending AortaElastinExtracellular MatrixFat DropletFinite Element AnalysisFoam CellHeart CycleImaging and DisplayImmunofluorescenceIntimaLipid CrystalLipid DietLipid StorageMaleMechanical StressMouseMultimodal Nonlinear Optical ImagingNon-HumanWestern Blotting
ISSN
0021-9150
Abstract
Objective: Although lipid crystals (LCs) have received attention as a causative factor of plaque rupture, the mechanisms by which they increase plaque vulnerability are unknown. We examined whether solid-state LCs physically affect the adjacent extracellular matrix (ECM) using a combination of multimodal nonlinear optical (MNLO) imaging and finite element analysis (FEA). Methods: The changes of ECMs affected by lipids in atherosclerotic arteries in apolipoprotein E-deficient mice (n=32) fed a high-fat diet for 20-30 weeks were micro-anatomically visualized by a 3D MNLO imaging platform including CARS for lipids, TPEF for elastin, and SHG for collagen. Results and Conclusion: The TPEF signal of elastin was increased at the peripheral regions of LCs (<10μm) compared with foam cell regions. In order to confirm the increase of elastin, biochemical assay (western blot) was performed. The protein level of elastin was increased approximately 2.25-fold (p=0.024) in LC-rich arteries. Under the hypothesis that the increase of elastin resulted from the mechanical stimulus from solid-state LCs, MNLO images were subjected to FEA to simulate the displacement according to the expanding magnitude of the vessel during cardiac cycles. We found that microscale focal stress was increased specifically around the LCs. These FEA results corresponded with the increase of elastin observed by TPEF. These data suggest that LCs mechanically stimulate the adjacent ECM to alter the composition of ECM and cause vessel remodeling. The combination of MNLO imaging and FEA has great potential to verify the mechanical predictions in cardiovascular diseases. © 2014 Elsevier Ireland Ltd.
URI
http://hdl.handle.net/20.500.11750/2996
DOI
10.1016/j.atherosclerosis.2014.10.018
Publisher
Elsevier Ltd
Related Researcher
Files:
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Collection:
New BiologyETC1. Journal Articles


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