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Immunization of apoE-/- mice with aldehyde-modified fibronectin inhibits the development of atherosclerosis.

Dunér, Pontus LU ; To, Fong LU ; Beckmann, Karsten; Björkbacka, Harry LU ; Nordin Fredrikson, Gunilla LU ; Nilsson, Jan LU and Bengtsson, Eva LU (2011) In Cardiovascular Research 91(3). p.528-536
Abstract
Aims. Oxidation of LDL in the extracellular matrix of the arterial wall results in formation of malondialdehyde (MDA) that modifies surrounding matrix proteins. This is associated with activation of an immune response against modified extracellular matrix proteins present in atherosclerotic plaques. Clinical studies have revealed an inverse association between antibodies to MDA-modified fibronectin and risk for development of cardiovascular events. To determine the functional role of these immune responses in atherosclerosis we performed studies in which apoE-deficient mice were immunized with MDA-modified fibronectin. Methods and Results. Immunization of apoE-deficient mice with MDA-modified fibronectin resulted in a 70% decrease in... (More)
Aims. Oxidation of LDL in the extracellular matrix of the arterial wall results in formation of malondialdehyde (MDA) that modifies surrounding matrix proteins. This is associated with activation of an immune response against modified extracellular matrix proteins present in atherosclerotic plaques. Clinical studies have revealed an inverse association between antibodies to MDA-modified fibronectin and risk for development of cardiovascular events. To determine the functional role of these immune responses in atherosclerosis we performed studies in which apoE-deficient mice were immunized with MDA-modified fibronectin. Methods and Results. Immunization of apoE-deficient mice with MDA-modified fibronectin resulted in a 70% decrease in plaque area and a less inflammatory phenotype of remaining plaques. Immunization shifted a weak naturally occurring Th1 antibody response against MDA-fibronectin into a Th2 antibody response. Cytokine expression and flow cytometry analyses of spleen cells from immunized mice showed an activation of regulatory T cells. Immunization with MDA-fibronectin was also found to reduce plasma fibronectin levels. Conclusions. Immunization with MDA-fibronectin significantly reduces the development of atherosclerosis in apoE-deficient mice suggesting that the immune response observed in humans may have a protective effect. MDA-fibronectin represents a possible novel target for immunomodulatory therapy in atherosclerosis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Immunization, ApoE(-/-) mice, Atherosclerosis, MDA-fibronectin
in
Cardiovascular Research
volume
91
issue
3
pages
528 - 536
publisher
Elsevier
external identifiers
  • wos:000293075200022
  • pmid:21493703
  • scopus:79960802275
ISSN
1755-3245
DOI
10.1093/cvr/cvr101
language
English
LU publication?
yes
id
56f9d44b-b706-4641-9bd0-6a9ebe8be1aa (old id 1937091)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21493703?dopt=Abstract
date added to LUP
2011-05-02 14:32:54
date last changed
2017-11-05 03:17:46
@article{56f9d44b-b706-4641-9bd0-6a9ebe8be1aa,
  abstract     = {Aims. Oxidation of LDL in the extracellular matrix of the arterial wall results in formation of malondialdehyde (MDA) that modifies surrounding matrix proteins. This is associated with activation of an immune response against modified extracellular matrix proteins present in atherosclerotic plaques. Clinical studies have revealed an inverse association between antibodies to MDA-modified fibronectin and risk for development of cardiovascular events. To determine the functional role of these immune responses in atherosclerosis we performed studies in which apoE-deficient mice were immunized with MDA-modified fibronectin. Methods and Results. Immunization of apoE-deficient mice with MDA-modified fibronectin resulted in a 70% decrease in plaque area and a less inflammatory phenotype of remaining plaques. Immunization shifted a weak naturally occurring Th1 antibody response against MDA-fibronectin into a Th2 antibody response. Cytokine expression and flow cytometry analyses of spleen cells from immunized mice showed an activation of regulatory T cells. Immunization with MDA-fibronectin was also found to reduce plasma fibronectin levels. Conclusions. Immunization with MDA-fibronectin significantly reduces the development of atherosclerosis in apoE-deficient mice suggesting that the immune response observed in humans may have a protective effect. MDA-fibronectin represents a possible novel target for immunomodulatory therapy in atherosclerosis.},
  author       = {Dunér, Pontus and To, Fong and Beckmann, Karsten and Björkbacka, Harry and Nordin Fredrikson, Gunilla and Nilsson, Jan and Bengtsson, Eva},
  issn         = {1755-3245},
  keyword      = {Immunization,ApoE(-/-) mice,Atherosclerosis,MDA-fibronectin},
  language     = {eng},
  number       = {3},
  pages        = {528--536},
  publisher    = {Elsevier},
  series       = {Cardiovascular Research},
  title        = {Immunization of apoE-/- mice with aldehyde-modified fibronectin inhibits the development of atherosclerosis.},
  url          = {http://dx.doi.org/10.1093/cvr/cvr101},
  volume       = {91},
  year         = {2011},
}