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Plasma fibronectin deficiency impedes atherosclerosis progression and fibrous cap formation

Rohwedder, Ina; Montanez, Eloi; Beckmann, Karsten; Bengtsson, Eva LU ; Dunér, Pontus LU ; Nilsson, Jan LU ; Soehnlein, Oliver and Faessler, Reinhard (2012) In EMBO Molecular Medicine 4(7). p.564-576
Abstract
Atherosclerotic lesions are asymmetric focal thickenings of the intima of arteries that consist of lipids, various cell types and extracellular matrix (ECM). These lesions lead to vascular occlusion representing the most common cause of death in the Western world. The main cause of vascular occlusion is rupture of atheromatous lesions followed by thrombus formation. Fibronectin (FN) is one of the earliest ECM proteins deposited at atherosclerosis-prone sites and was suggested to promote atherosclerotic lesion formation. Here, we report that atherosclerosis-prone apolipoprotein E-null mice lacking hepatocyte-derived plasma FN (pFN) fed with a pro-atherogenic diet display dramatically reduced FN depositions at atherosclerosis-prone areas,... (More)
Atherosclerotic lesions are asymmetric focal thickenings of the intima of arteries that consist of lipids, various cell types and extracellular matrix (ECM). These lesions lead to vascular occlusion representing the most common cause of death in the Western world. The main cause of vascular occlusion is rupture of atheromatous lesions followed by thrombus formation. Fibronectin (FN) is one of the earliest ECM proteins deposited at atherosclerosis-prone sites and was suggested to promote atherosclerotic lesion formation. Here, we report that atherosclerosis-prone apolipoprotein E-null mice lacking hepatocyte-derived plasma FN (pFN) fed with a pro-atherogenic diet display dramatically reduced FN depositions at atherosclerosis-prone areas, which results in significantly smaller and fewer atherosclerotic plaques. However, the atherosclerotic lesions from pFN-deficient mice lacked vascular smooth muscle cells and failed to develop a fibrous cap. Thus, our results demonstrate that while FN worsens the course of atherosclerosis by increasing the atherogenic plaque area, it promotes the formation of the protective fibrous cap, which in humans prevents plaques rupture and vascular occlusion. See accompanying article http://dx.doi.org/10.1002/emmm.201200238 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atherosclerosis, fibronectin, fibrous cap, inflammation, migration
in
EMBO Molecular Medicine
volume
4
issue
7
pages
564 - 576
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000305943600007
  • scopus:84863467640
ISSN
1757-4684
DOI
10.1002/emmm.201200237
language
English
LU publication?
yes
id
37df6585-b967-4df0-b68d-abe4e4a9b708 (old id 3001455)
date added to LUP
2012-09-03 07:20:19
date last changed
2017-09-24 03:03:30
@article{37df6585-b967-4df0-b68d-abe4e4a9b708,
  abstract     = {Atherosclerotic lesions are asymmetric focal thickenings of the intima of arteries that consist of lipids, various cell types and extracellular matrix (ECM). These lesions lead to vascular occlusion representing the most common cause of death in the Western world. The main cause of vascular occlusion is rupture of atheromatous lesions followed by thrombus formation. Fibronectin (FN) is one of the earliest ECM proteins deposited at atherosclerosis-prone sites and was suggested to promote atherosclerotic lesion formation. Here, we report that atherosclerosis-prone apolipoprotein E-null mice lacking hepatocyte-derived plasma FN (pFN) fed with a pro-atherogenic diet display dramatically reduced FN depositions at atherosclerosis-prone areas, which results in significantly smaller and fewer atherosclerotic plaques. However, the atherosclerotic lesions from pFN-deficient mice lacked vascular smooth muscle cells and failed to develop a fibrous cap. Thus, our results demonstrate that while FN worsens the course of atherosclerosis by increasing the atherogenic plaque area, it promotes the formation of the protective fibrous cap, which in humans prevents plaques rupture and vascular occlusion. See accompanying article http://dx.doi.org/10.1002/emmm.201200238},
  author       = {Rohwedder, Ina and Montanez, Eloi and Beckmann, Karsten and Bengtsson, Eva and Dunér, Pontus and Nilsson, Jan and Soehnlein, Oliver and Faessler, Reinhard},
  issn         = {1757-4684},
  keyword      = {atherosclerosis,fibronectin,fibrous cap,inflammation,migration},
  language     = {eng},
  number       = {7},
  pages        = {564--576},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {EMBO Molecular Medicine},
  title        = {Plasma fibronectin deficiency impedes atherosclerosis progression and fibrous cap formation},
  url          = {http://dx.doi.org/10.1002/emmm.201200237},
  volume       = {4},
  year         = {2012},
}