Using a novel experimental model, ISD researchers showed that stroke activates the AIM2 inflammasome in atherosclerotic plaques via increased circulating cell-free DNA, causing inflammation, plaque destabilization, and recurrent stroke. Neutrophil NETosis was identified as the main source of cell-free DNA. Neutralizing cell-free DNA or inhibiting inflammasome activation reduced stroke recurrence, offering new perspectives for the prevention of early recurrent events.
Cao J, Roth S, Zhang S, Kopczak A, Mami S, Asare Y, Georgakis MK, Messerer D, Horn A, Shemer R, Jacqmarcq C, Picot A, Green JP, Schlegl C, Li X, Tomas L, Dutsch A, Liman TG, Endres M, Wernsdorf SR, Fürle C, Carofiglio O, Zhu J, Brough D; DEMDAS Study Group; Hornung V, Dichgans M, Vivien D, Schulz C, Dor Y, Tiedt S, Sager HB, Grosse GM, Liesz A. DNA-sensing inflammasomes cause recurrent atherosclerotic stroke. Nature. 2024 Aug 7. doi: 10.1038/s41586-024-07803-4. Epub ahead of print.