LAUSR

Stroke is associated with acute and chronic inflammatory responses, and epidemiological studies have shown that patients who experience a stroke as a result of underlying atherosclerosis are at substantially increased risk of recurrent stroke events. Arthur Liesz and colleagues now show that the immune response triggered by stroke can cause atherosclerotic plaque progression. Apoe–/– mice were fed a highcholesterol diet and then underwent either surgery to induce a stroke or a sham procedure. Both atherosclerotic plaque load and monocyte cell counts were higher in the aorta of mice after stroke compared with control. The C-C motif chemokine 2 pathway was critical in attracting pro-inflammatory monocytes to the aorta after stroke. Additionally, plaques had a more vulnerable morphology after stroke, indicated by increased activity of metalloproteinases 2 and 9 and reduced thickness of the fibrous cap. Acute stroke produces a massive release of pro-inflammatory alarmin proteins, such as high mobility group protein B1 (HMGB1), from hypoxic and necrotic brain tissue. HMGB1 induced monocyte and endothelial activation via receptor for advanced glycosylation end products (RAGE) signalling. The investigators showed that reducing systemic levels of alarmins using a soluble form of RAGE as a decoy receptor reduced atherosclerotic A T H E R O S C L E R O S I S