Increased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency.
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Conrad, Daniel H
Binder, Christoph J
Lippincott Williams & Wilkins Ltd.
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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.. Circulation research, 120 (1), 78-84. https://doi.org/10.1161/circresaha.116.309606
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.
Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Immunoglobulin E, Immunoglobulin M, Male, Atherosclerosis, Mice, 129 Strain, Biomarkers
British Heart Foundation (RG/10/001/27643)
External DOI: https://doi.org/10.1161/circresaha.116.309606
This record's URL: https://www.repository.cam.ac.uk/handle/1810/291930