Roth, Stefan; Singh, Vikramjeet; Tiedt, Steffen; Schindler, Lisa; Huber, Georg; Geerlof, Arie; Antoine, Daniel J; Anfray, Antoine; Orset, Cyrille; Gauberti, Maxime; Fournier, Antoine; Holdt, Lesca M; Harris, Helena Erlandsson; Engelhardt, Britta; Bianchi, Marco E; Vivien, Denis; Haffner, Christof; Bernhagen, Jürgen; Dichgans, Martin and Liesz, Arthur (2018). Brain-released alarmins and stress response synergize in accelerating atherosclerosis progression after stroke. Science translational medicine, 10(432) American Association for the Advancement of Science 10.1126/scitranslmed.aao1313
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Stroke induces a multiphasic systemic immune response, but the consequences of this response on atherosclerosis-a major source of recurrent vascular events-have not been thoroughly investigated. We show that stroke exacerbates atheroprogression via alarmin-mediated propagation of vascular inflammation. The prototypic brain-released alarmin high-mobility group box 1 protein induced monocyte and endothelial activation via the receptor for advanced glycation end products (RAGE)-signaling cascade and increased plaque load and vulnerability. Recruitment of activated monocytes via the CC-chemokine ligand 2-CC-chemokine receptor type 2 pathway was critical in stroke-induced vascular inflammation. Neutralization of circulating alarmins or knockdown of RAGE attenuated atheroprogression. Blockage of β3-adrenoreceptors attenuated the egress of myeloid monocytes after stroke, whereas neutralization of circulating alarmins was required to reduce systemic monocyte activation and aortic invasion. Our findings identify a synergistic effect of the sympathetic stress response and alarmin-driven inflammation via RAGE as a critical mechanism of exacerbated atheroprogression after stroke.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute |
UniBE Contributor: |
Engelhardt, Britta |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
1946-6234 |
Publisher: |
American Association for the Advancement of Science |
Language: |
English |
Submitter: |
Ursula Zingg-Zünd |
Date Deposited: |
25 Feb 2019 16:25 |
Last Modified: |
05 Dec 2022 15:24 |
Publisher DOI: |
10.1126/scitranslmed.aao1313 |
PubMed ID: |
29540615 |
BORIS DOI: |
10.7892/boris.124098 |
URI: |
https://boris.unibe.ch/id/eprint/124098 |
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