Inflammasome-Driven Interleukin-1α and Interleukin-1β Production in Atherosclerotic Plaques Relates to Hyperlipidemia and Plaque Complexity.

•Genetic and functional evidence suggests that there are additional inflammasome pathways, besides NLRP3, that contribute to IL-1 generation in human atherosclerotic plaques.•Plaque generation of mature IL-1β is accompanied by secretion of similar levels of IL-1α, through a mechanism controlled by NLRP3 and caspase-1.•Plaque IL-1β production is higher in patients with uncontrolled hyperlipidemia, on no or low-dose statin therapy, or with complex plaque imaging features.•The present study lends support to high-intensity cholesterol lowering and anti-IL-1-directed therapies for patients at high cardiovascular risk.