Send to

Choose Destination
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

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


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.


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

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center