-
Tytuł:
-
Alarmin-activated B cells accelerate murine atherosclerosis after myocardial infarction via plasma cell-immunoglobulin-dependent mechanisms.
-
Autorzy:
-
Kyaw T; Vascular Biology and Atherosclerosis, Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC 3004, Australia.; Centre for Inflammatory Diseases, Department of Medicine, Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia.
Loveland P; Vascular Biology and Atherosclerosis, Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC 3004, Australia.
Kanellakis P; Vascular Biology and Atherosclerosis, Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC 3004, Australia.
Cao A; Vascular Biology and Atherosclerosis, Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC 3004, Australia.; Centre for Inflammatory Diseases, Department of Medicine, Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia.
Kallies A; Department of Microbiology and Immunology, University of Melbourne, 792 Elizabeth Street, Melbourne, Vic 3000, Australia.
Huang AL; Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC 3004, Australia.; Department of Cardiology, Alfred Hospital, 55 Commercial Rd, Melbourne, VIC 3004, Australia.
Peter K; Atherothrombosis and Vascular Biology, Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC 3004, Australia.; Department of Cardiology, Alfred Hospital, 55 Commercial Rd, Melbourne, VIC 3004, Australia.; Department of Immunology, Central Clinical School, 99 Commercial Rd, Melbourne, VIC 3004, Australia.
Toh BH; Centre for Inflammatory Diseases, Department of Medicine, Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia.
Bobik A; Vascular Biology and Atherosclerosis, Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC 3004, Australia.; Centre for Inflammatory Diseases, Department of Medicine, Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia.; Department of Immunology, Central Clinical School, 99 Commercial Rd, Melbourne, VIC 3004, Australia.
-
Źródło:
-
European heart journal [Eur Heart J] 2021 Mar 01; Vol. 42 (9), pp. 938-947.
-
Typ publikacji:
-
Journal Article; Research Support, Non-U.S. Gov't
-
Język:
-
English
-
Imprint Name(s):
-
Publication: 2005- : Oxford : Oxford University Press
Original Publication: London, Saunders [etc.]
-
MeSH Terms:
-
Alarmins*
Atherosclerosis*/etiology
B-Lymphocytes*
Myocardial Infarction*
Plaque, Atherosclerotic*
Animals ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; Mice, Knockout, ApoE ; Plasma Cells
-
Contributed Indexing:
-
Keywords: Accelerated atherosclerosis; Autoantibodies; B cells; Plasma cells; Myocardial infarction
-
Substance Nomenclature:
-
0 (Alarmins)
-
Entry Date(s):
-
Date Created: 20201218 Date Completed: 20210527 Latest Revision: 20220531
-
Update Code:
-
20240105
-
DOI:
-
10.1093/eurheartj/ehaa995
-
PMID:
-
33338208
-
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.
(Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)
Comment in: Eur Heart J. 2021 Mar 1;42(9):948-950. (PMID: 33394010)
Comment in: Nat Rev Cardiol. 2021 Apr;18(4):232. (PMID: 33462419)