Publication

Linking immune-mediated arterial inflammation and cholesterol-induced atherosclerosis in a transgenic mouse model

Journal Paper/Review - Nov 7, 2000

Units
PubMed
Doi

Citation
Ludewig B, Freigang S, Jäggi M, Kurrer M, Pei Y, Vlk L, Odermatt B, Zinkernagel R, Hengartner H. Linking immune-mediated arterial inflammation and cholesterol-induced atherosclerosis in a transgenic mouse model. Proceedings of the National Academy of Sciences of the United States of America 2000; 97:12752-7.
Type
Journal Paper/Review (English)
Journal
Proceedings of the National Academy of Sciences of the United States of America 2000; 97
Publication Date
Nov 7, 2000
Issn Print
0027-8424
Pages
12752-7
Brief description/objective

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.