Stroke alarmin spurs further embolies

In Science Translational Medicine, the team headed by Arthur Liesz from LMU Munich report that  the  alarmin protein HMGB1 (high mobility group box 1), which is released from damaged brain tissue following a stroke, and the activation of a stress response from the sympathetic nervous system, was sufficient to spur arterial plaque formation. The newly discovered link between stroke and atherosclerosis may for the first time explain why the induction of a multiphasic systemic immune response by stroke increases the risk of subsequent strokes and heart attack, which remains high in patients for years after experiencing the first stroke. 

The results also suggests that interfering with the signaling activated by HMGB1 could help reduce the risk of secondary cardiovascular diseases. Using mouse models, the research team found that HMGB1 released from brain tissue triggers monocyte and endothelial activation via the receptor for advanced glycation end products (RAGE)–signaling cascade that enhances inflammation in blood vessels, particularly by attracting proinflammatory monocytes to arterial plaque lesions. Recruitment of activated monocytes via the CC-chemokine ligand 2–CC-chemokine receptor type 2 pathway was critical in stroke-induced vascular inflammation. Neutralisation of circulating alarmins or knockdown of RAGE attenuated atheroprogression. Blockage of β3-adrenoreceptors attenuated the egress of myeloid monocytes after stroke, whereas neutralisation of circulating alarmins was required to reduce systemic monocyte activation and aortic invasion

The authors conclude that the inflammatory response acts in concert with an acute sympathetic stress response to accelerate the formation and the instability of atherosclerotic plaques. Liesz and colleagues say that neutralising brain-released alarmins may offer a therapeutic approach for stroke patients.