Immunization of apoE-/- mice with aldehyde-modified fibronectin inhibits the development of atherosclerosis.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1937091
- author
- Dunér, Pontus LU ; To, Fong LU ; Beckmann, Karsten ; Björkbacka, Harry LU ; Nordin Fredrikson, Gunilla LU ; Nilsson, Jan LU and Bengtsson, Eva LU
- organization
- publishing date
- 2011
- 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
- Oxford University Press
- external identifiers
-
- wos:000293075200022
- pmid:21493703
- scopus:79960802275
- pmid:21493703
- 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
- 2016-04-01 10:43:35
- date last changed
- 2022-01-26 01:58:22
@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}}, keywords = {{Immunization; ApoE(-/-) mice; Atherosclerosis; MDA-fibronectin}}, language = {{eng}}, number = {{3}}, pages = {{528--536}}, publisher = {{Oxford University Press}}, series = {{Cardiovascular Research}}, title = {{Immunization of apoE-/- mice with aldehyde-modified fibronectin inhibits the development of atherosclerosis.}}, url = {{https://lup.lub.lu.se/search/files/2084824/1971404.pdf}}, doi = {{10.1093/cvr/cvr101}}, volume = {{91}}, year = {{2011}}, }