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JACC Basic Transl Sci. 2019 Jun 24;4(3):304-317. doi: 10.1016/j.jacbts.2019.02.007. eCollection 2019 Jun.

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

Author information

1
Experimental Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
2
Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
3
Department of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden.

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.

KEYWORDS:

ASC, apoptosis-associated speck-like protein containing a CARD; ATP, adenosine 5′-triphosphate disodium salt hydrate; BiKE, Biobank of Karolinska Carotid Endarterectomies; CT, Computerized tomographic scanning; IL, interleukin; LDL, low-density lipoprotein; LPS, lipopolysaccharide; NLRC, nucleotide-binding oligomerization domain, leucine-rich repeat and CARD domain–containing protein; NLRP, nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain–containing protein; PBS, phosphate-buffered saline; atherosclerosis; hypercholesterolemia; inflammasome; inflammation; interleukin-1; mRNA, messenger ribonucleic acid

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