title: Lipid crystals mechanically stimulate adjacent extracellular matrix in advanced atherosclerotic plaques.
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.
  
  
  CONCLUSIONS
  The TPEF signal of elastin was increased at the peripheral regions of LCs (<10 μm) 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.
authors.affiliation: Center for Nanosafety Metrology, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea.
authors.forename: Eun-Soo
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Center for Nanosafety Metrology, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea; Department of Nanobio Surface Science, Korea University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Center for Nanosafety Metrology, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea.
authors.forename: Sang-Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Center for Energy Materials Metrology, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea.
authors.forename: Junhee
authors.initials: J
authors.lastname: Hahn
authors.affiliation: Department of Mechanical Engineering, Korea University, Seoul, Republic of Korea.
authors.forename: Haea
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Mechanical Engineering, Korea University, Seoul, Republic of Korea.
authors.forename: Soo-Won
authors.initials: SW
authors.lastname: Chae
authors.affiliation: Center for Nanosafety Metrology, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea; Department of Nanobio Surface Science, Korea University of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Tae Geol
authors.initials: TG
authors.lastname: Lee
authors.affiliation: Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Moon
authors.affiliation: Center for Nanosafety Metrology, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea; Department of Nanobio Surface Science, Korea University of Science and Technology, Daejeon, Republic of Korea. Electronic address: shkim@kriss.re.kr.
authors.forename: Se-Hwa
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D003460:Crystallization; D059305:Diet, High-Fat; D004549:Elastin / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D020342:Finite Element Analysis; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000473:pathology; D055095:Optics and Photonics; D058226:Plaque, Atherosclerotic / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E; D008055:Lipids; D003094:Collagen; D004549:Elastin
keywords: Elastin; Finite element analysis; Foam cell; Lipid crystal; Multimodal nonlinear optical imaging