Document Detail


Linking immune-mediated arterial inflammation and cholesterol-induced atherosclerosis in a transgenic mouse model.
MedLine Citation:
PMID:  11050173     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Arterial inflammatory responses are thought to be a significant component of atherosclerotic disease. We describe here, using a transgenic approach, the mutual perpetuation of immune-mediated arterial inflammation and cholesterol-induced atherosclerosis. Mice expressing the bacterial transgene beta-galactosidase exclusively in cardiomyocytes and in smooth muscle cells in lung arteries and the aorta (SM-LacZ), and hypercholesterolemic apolipoprotein E-deficient SM-LacZ mice (SM-LacZ/apoE(-/-)) developed myocarditis and arteritis after immunization with dendritic cells presenting a beta-galactosidase-derived immunogenic peptide. Hypercholesterolemia amplified acute arteritis and perpetuated chronic arterial inflammation in SM-LacZ/apoE(-/-) mice, but had no major impact on acute myocarditis or the subsequent development of dilated cardiomyopathy. Conversely, arteritis significantly accelerated cholesterol-induced atherosclerosis. Taken together, these data demonstrate that the linkage of immune-mediated arteritis and hypercholesterolemia favors initiation and maintenance of atherosclerotic lesion formation. Therapeutic strategies to prevent or disrupt such self-perpetuating vicious circles may be crucial for the successful treatment of atherosclerosis.
Authors:
B Ludewig; S Freigang; M Jäggi; M O Kurrer; Y C Pei; L Vlk; B Odermatt; R M Zinkernagel; H Hengartner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  97     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-11-27     Completed Date:  2001-01-11     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  12752-7     Citation Subset:  IM    
Affiliation:
Institute of Experimental Immunology, Department of Pathology, and Institute for Clinical Chemistry, University Hospital Zurich, University of Zurich, Zurich, Switzerland. ludewigb@pathol.unizh.ch
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta / immunology*,  pathology
Arteriosclerosis / etiology,  immunology*,  metabolism
Cholesterol / immunology*,  metabolism
Dendritic Cells / immunology
Female
Hypercholesterolemia / immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Pulmonary Artery / immunology*,  pathology
Chemical
Reg. No./Substance:
57-88-5/Cholesterol
Comments/Corrections

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