Immunization of apoE-/- mice with aldehyde-modified fibronectin inhibits the development of atherosclerosis.
Författare
Summary, in English
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.
Avdelning/ar
Publiceringsår
2011
Språk
Engelska
Sidor
528-536
Publikation/Tidskrift/Serie
Cardiovascular Research
Volym
91
Issue
3
Fulltext
- Available as PDF - 13 MB
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Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Oxford University Press
Ämne
- Cardiac and Cardiovascular Systems
Nyckelord
- Immunization
- ApoE(-/-) mice
- Atherosclerosis
- MDA-fibronectin
Status
Published
Forskningsgrupp
- Cardiovascular Research - Immunity and Atherosclerosis
ISBN/ISSN/Övrigt
- ISSN: 1755-3245