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

ABSTRACT: CANTOS (Canakinumab Antiinflammatory Thrombosis Outcome Study) confirmed interleukin (IL)-1? as an appealing therapeutic target for human atherosclerosis and related complications. However, there are serious gaps in our understanding of IL-1 production in atherosclerosis. Herein the authors show that complex plaques, or plaques derived from patients with suboptimally controlled hyperlipidemia, or on no or low-intensity statin therapy, demonstrated higher recruitable IL-1? production. Generation of mature IL-1? was matched by IL-1? release, and both were attenuated by inhibition of NLR family pyrin domain containing 3 or caspase. These findings support the inflammasome as the main pathway for IL-1?/? generation in atherosclerosis and high-intensity lipid-lowering therapies as primary and additional anti-IL-1-directed therapies as secondary interventions in high-risk patients.

SUBMITTER: Jiang X 

PROVIDER: S-EPMC6610158 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature