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Fibromodulin Deficiency Reduces Low-Density Lipoprotein Accumulation in Atherosclerotic Plaques in Apolipoprotein E-Null Mice.

Shami, Annelie LU ; Gustafsson, Renata LU ; Kalamajski, Sebastian LU ; Krams, Rob; Segers, Dolf; Rauch, Uwe LU ; Roos, Gunnel LU ; Nilsson, Jan LU ; Oldberg, Åke LU and Hultgårdh, Anna LU (2012) In Arteriosclerosis, Thrombosis and Vascular Biology
Abstract
OBJECTIVE: The aim of this study was to analyze how an altered collagen structure affects development of atherosclerotic plaques. METHODS AND RESULTS: Fibromodulin-null mice develop an abnormal collagen fibril structure. In apolipoprotein E (ApoE)-null and ApoE/fibromodulin-null mice, a shear stress-modifying carotid artery cast induced formation of atherosclerotic plaques of different phenotypes; inflammatory in low-shear stress regions and fibrous in oscillatory shear stress regions. Electron microscopy showed that collagen fibrils were thicker and more heterogeneous in oscillatory shear stress lesions from ApoE/fibromodulin-null mice. Low-shear stress lesions were smaller in ApoE/fibromodulin-null mice and contained less lipids. Total... (More)
OBJECTIVE: The aim of this study was to analyze how an altered collagen structure affects development of atherosclerotic plaques. METHODS AND RESULTS: Fibromodulin-null mice develop an abnormal collagen fibril structure. In apolipoprotein E (ApoE)-null and ApoE/fibromodulin-null mice, a shear stress-modifying carotid artery cast induced formation of atherosclerotic plaques of different phenotypes; inflammatory in low-shear stress regions and fibrous in oscillatory shear stress regions. Electron microscopy showed that collagen fibrils were thicker and more heterogeneous in oscillatory shear stress lesions from ApoE/fibromodulin-null mice. Low-shear stress lesions were smaller in ApoE/fibromodulin-null mice and contained less lipids. Total plaque burden in aortas stained en face with Oil Red O, as well as lipid accumulation in aortic root lesions, was also decreased in ApoE/fibromodulin-null mice. In addition, lipid accumulation in RAW264.7 macrophages cultured on fibromodulin-deficient extracellular matrix was decreased, whereas levels of interleukin-6 and -10 were increased. Our results show that an abnormal plaque collagen fibril structure can influence atherosclerotic plaque development. CONCLUSIONS: The present findings suggest a more complex role for collagen in plaque stability than previously anticipated, in that it may promote lipid-accumulation and inflammation at the same time as it provides mechanical stability. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Arteriosclerosis, Thrombosis and Vascular Biology
publisher
American Heart Association
external identifiers
  • wos:000313747700030
  • pmid:23202368
  • scopus:84872893409
ISSN
1524-4636
DOI
10.1161/ATVBAHA.112.300723
language
English
LU publication?
yes
id
4da0bcf8-7252-4069-8cc1-9c56b4eb5c54 (old id 3347728)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23202368?dopt=Abstract
date added to LUP
2013-01-02 11:59:23
date last changed
2017-10-01 03:12:58
@article{4da0bcf8-7252-4069-8cc1-9c56b4eb5c54,
  abstract     = {OBJECTIVE: The aim of this study was to analyze how an altered collagen structure affects development of atherosclerotic plaques. METHODS AND RESULTS: Fibromodulin-null mice develop an abnormal collagen fibril structure. In apolipoprotein E (ApoE)-null and ApoE/fibromodulin-null mice, a shear stress-modifying carotid artery cast induced formation of atherosclerotic plaques of different phenotypes; inflammatory in low-shear stress regions and fibrous in oscillatory shear stress regions. Electron microscopy showed that collagen fibrils were thicker and more heterogeneous in oscillatory shear stress lesions from ApoE/fibromodulin-null mice. Low-shear stress lesions were smaller in ApoE/fibromodulin-null mice and contained less lipids. Total plaque burden in aortas stained en face with Oil Red O, as well as lipid accumulation in aortic root lesions, was also decreased in ApoE/fibromodulin-null mice. In addition, lipid accumulation in RAW264.7 macrophages cultured on fibromodulin-deficient extracellular matrix was decreased, whereas levels of interleukin-6 and -10 were increased. Our results show that an abnormal plaque collagen fibril structure can influence atherosclerotic plaque development. CONCLUSIONS: The present findings suggest a more complex role for collagen in plaque stability than previously anticipated, in that it may promote lipid-accumulation and inflammation at the same time as it provides mechanical stability.},
  author       = {Shami, Annelie and Gustafsson, Renata and Kalamajski, Sebastian and Krams, Rob and Segers, Dolf and Rauch, Uwe and Roos, Gunnel and Nilsson, Jan and Oldberg, Åke and Hultgårdh, Anna},
  issn         = {1524-4636},
  language     = {eng},
  month        = {11},
  publisher    = {American Heart Association},
  series       = {Arteriosclerosis, Thrombosis and Vascular Biology},
  title        = {Fibromodulin Deficiency Reduces Low-Density Lipoprotein Accumulation in Atherosclerotic Plaques in Apolipoprotein E-Null Mice.},
  url          = {http://dx.doi.org/10.1161/ATVBAHA.112.300723},
  year         = {2012},
}