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

作者：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 Juergen; Dichgans Martin; Liesz Arthur^*

来源：Science Translational Medicine, 2018, 10(432): eaao1313.

DOI：10.1126/scitranslmed.aao1313

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.

• 出版日期2018-3-14