Brain-released alarmins and stress response synergize in accelerating atherosclerosis progression after stroke

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 und Liesz, Arthur (2018): Brain-released alarmins and stress response synergize in accelerating atherosclerosis progression after stroke. In: Science Translational Medicine, Bd. 10, Nr. 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Institut für Schlaganfall- und Demenzforschung (ISD)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1946-6234
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198