ORCID: https://orcid.org/0000-0002-0654-387X und Liesz, Arthur
(2018):
Brain-released alarmins and stress response synergize in accelerating atherosclerosis progression after stroke.
In: Science Translational Medicine, Vol. 10, No. 432, eaao1313
Abstract
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. 3-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 |
|---|---|
| Faculties: | Medicine > Munich Cluster for Systems Neurology (SyNergy) Medicine > Institute for Stroke and Dementia Research (ISD) |
| Subjects: | 600 Technology > 610 Medicine and health |
| ISSN: | 1946-6234 |
| Language: | English |
| Item ID: | 62968 |
| Date Deposited: | 19. Jul 2019 12:12 |
| Last Modified: | 06. Jun 2024 12:52 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
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