Increased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency.
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Authors
Tsiantoulas, Dimitrios
Bot, Ilze
Ozsvar-Kozma, Maria
Göderle, Laura
Perkmann, Thomas
Hartvigsen, Karsten
Conrad, Daniel H
Kuiper, Johan
Binder, Christoph J
Publication Date
2017-01-06Journal Title
Circ Res
ISSN
0009-7330
Publisher
Ovid Technologies (Wolters Kluwer Health)
Volume
120
Issue
1
Pages
78-84
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Tsiantoulas, D., Bot, I., Ozsvar-Kozma, M., Göderle, L., Perkmann, T., Hartvigsen, K., Conrad, D. H., et al. (2017). Increased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency.. Circ Res, 120 (1), 78-84. https://doi.org/10.1161/CIRCRESAHA.116.309606
Abstract
RATIONALE: Deficiency of secreted IgM (sIgM-/-) accelerates atherosclerosis in Ldlr-/-mice. Several atheroprotective effects of increased levels of IgM antibodies have been suggested, including preventing inflammation induced by oxidized low-density lipoprotein and promoting apoptotic cell clearance. However, the mechanisms by which the lack of sIgM promotes lesion formation remain unknown. OBJECTIVE: To identify the mechanisms by which sIgM deficiency accelerates atherosclerosis in mice. METHODS AND RESULTS: We here show that both sIgM-/- and Ldlr-/-sIgM-/- mice develop increased plasma IgE titers because of impaired generation of B cells expressing the low-affinity IgE receptor CD23, which mediates the clearance of IgE antibodies. We further report that Ldlr-/-sIgM-/- mice exhibit increased numbers of activated mast cells and neutrophils in the perivascular area of atherosclerotic plaques. Treatment with an anti-IgE-neutralizing antibody fully reversed vascular inflammation and accelerated atherosclerotic lesion formation in cholesterol-fed Ldlr-/-sIgM-/- mice. CONCLUSIONS: Thus, our data identify a previously unsuspected mechanism by which sIgM deficiency aggravates atherosclerosis.
Keywords
Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Immunoglobulin E, Immunoglobulin M, Male, Atherosclerosis, Mice, 129 Strain, Biomarkers
Sponsorship
British Heart Foundation (None)
Identifiers
External DOI: https://doi.org/10.1161/CIRCRESAHA.116.309606
This record's URL: https://www.repository.cam.ac.uk/handle/1810/291930
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