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

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

Xintong Jiang, Feilong Wang, Yajuan Wang, Anton Gisterå, Joy Roy, Gabrielle Paulsson-Berne, Ulf Hedin, Amir Lerman, Göran K Hansson, Joerg Herrmann, Zhong-Qun Yan

JACC Basic Transl Sci. 2019 Jun 24;4(3):304-317.

PMID: 31312755

Abstract:

CANTOS (Canakinumab Antiinflammatory Thrombosis Outcome Study) confirmed interleukin (IL)-1β 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-1β production. Generation of mature IL-1β was matched by IL-1α 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-1α/β 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP34369078	Adenosine 5′-triphosphate disodium salt hydrate		34369-07-8	Price

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