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 journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)769-776
Number of pages8
JournalAtherosclerosis
Volume237
Issue number2
DOIs
Publication statusPublished - 2014 Dec 1

Fingerprint

Atherosclerotic Plaques
Extracellular Matrix
Elastin
Lipids
Finite Element Analysis
Optical Imaging
Arteries
Foam Cells
High Fat Diet
Apolipoproteins E
Rupture
Cardiovascular Diseases
Collagen
Western Blotting

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Lipid crystals mechanically stimulate adjacent extracellular matrix in advanced atherosclerotic plaques. / Lee, Eun Soo; Park, Joo Hyun; Lee, Sang Won; Hahn, Junhee; Lee, Haea; Chae, Soo Won; Lee, Tae Geol; Moon, Dae Won; Kim, Se Hwa.

In: Atherosclerosis, Vol. 237, No. 2, 01.12.2014, p. 769-776.

Research output: Contribution to journalArticle

Lee, Eun Soo ; Park, Joo Hyun ; Lee, Sang Won ; Hahn, Junhee ; Lee, Haea ; Chae, Soo Won ; Lee, Tae Geol ; Moon, Dae Won ; Kim, Se Hwa. / Lipid crystals mechanically stimulate adjacent extracellular matrix in advanced atherosclerotic plaques. In: Atherosclerosis. 2014 ; Vol. 237, No. 2. pp. 769-776.
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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.",
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AU - Park, Joo Hyun

AU - Lee, Sang Won

AU - Hahn, Junhee

AU - Lee, Haea

AU - Chae, Soo Won

AU - Lee, Tae Geol

AU - Moon, Dae Won

AU - Kim, Se Hwa

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N2 - 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.

AB - 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.

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