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• W3109013973 startingPage "938" @default.
• W3109013973 abstract "Abstract Aims Myocardial infarction (MI) accelerates atherosclerosis and greatly increases the risk of recurrent cardiovascular events for many years, in particular, strokes and MIs. Because B cell-derived autoantibodies produced in response to MI also persist for years, we investigated the role of B cells in adaptive immune responses to MI. Methods and results We used an apolipoprotein-E-deficient (ApoE−/−) mouse model of MI-accelerated atherosclerosis to assess the importance of B cells. One week after inducing MI in atherosclerotic mice, we depleted B cells using an anti-CD20 antibody. This treatment prevented subsequent immunoglobulin G accumulation in plaques and MI-induced accelerated atherosclerosis. In gain of function experiments, we purified spleen B cells from mice 1 week after inducing MI and transferred these cells into atherosclerotic ApoE−/− mice, which greatly increased immunoglobulin G (IgG) accumulation in plaque and accelerated atherosclerosis. These B cells expressed many cytokines that promote humoural immunity and in addition, they formed germinal centres within the spleen where they differentiated into antibody-producing plasma cells. Specifically deleting Blimp-1 in B cells, the transcriptional regulator that drives their terminal differentiation into antibody-producing plasma cells prevented MI-accelerated atherosclerosis. Alarmins released from infarcted hearts were responsible for activating B cells via toll-like receptors and deleting MyD88, the canonical adaptor protein for inflammatory signalling downstream of toll-like receptors, prevented B-cell activation and MI-accelerated atherosclerosis. Conclusion Our data implicate early B-cell activation and autoantibodies as a central cause for accelerated atherosclerosis post-MI and identifies novel therapeutic strategies towards preventing recurrent cardiovascular events such as MI and stroke." @default.
• W3109013973 created "2020-12-07" @default.
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• W3109013973 date "2020-12-18" @default.
• W3109013973 modified "2023-10-18" @default.
• W3109013973 title "Alarmin-activated B cells accelerate murine atherosclerosis after myocardial infarction via plasma cell-immunoglobulin-dependent mechanisms" @default.
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• W3109013973 doi "https://doi.org/10.1093/eurheartj/ehaa995" @default.
• W3109013973 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33338208" @default.
• W3109013973 hasPublicationYear "2020" @default.
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