Lipid crystals mechanically stimulate adjacent extracellular matrix in advanced atherosclerotic plaques

Eun Soo Lee, Joo Hyun Park, Sang Won Lee, Junhee Hahn, Haea Lee, Soo Won Chae, Tae Geol Lee, Dae Won Moon, Se Hwa Kim

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)769-776
Number of pages8
Issue number2
Publication statusPublished - 2014 Dec 1

Bibliographical note

Funding Information:
This research was supported by grants from the Development of NanoBio Convergence Technology (KRISS 2014-14011019 ) of the Korea Research Institute of Standards and Science ; the Pioneer Research Program ( 2012-0009541 ) funded by the Korean Ministry of Education, Science, and Technology ; and the Basic Science Research Program ( 2007-0056094 ) of the National Research Foundation, funded by the Ministry of Science, ICT, and Future Planning .

Publisher Copyright:
© 2014 Elsevier Ireland Ltd.


  • Elastin
  • Finite element analysis
  • Foam cell
  • Lipid crystal
  • Multimodal nonlinear optical imaging

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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