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

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

JACC: Basic to Translational Science (Jun 2019)

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

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

Affiliations

Xintong Jiang, MD: Experimental Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Feilong Wang, MD: Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
Yajuan Wang, MD, PhD: Experimental Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Anton Gisterå, MD, PhD: Experimental Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Joy Roy, MD, PhD: Department of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden
Gabrielle Paulsson-Berne, PhD: Experimental Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Ulf Hedin, MD, PhD: Department of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden
Amir Lerman, MD: Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
Göran K. Hansson, MD, PhD: Experimental Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Joerg Herrmann, MD: Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota; Address for correspondence: Dr. Joerg Herrmann, Department of Cardiovascular Diseases, Mayo Clinic, 200 1st Street, Southwest, Rochester, Minnesota 55905.
Zhong-qun Yan, MD, PhD: Experimental Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Dr. Zhong-qun Yan, Center for Molecular Medicine L8:03, Karolinska University Hospital, 171 76, Stockholm, Sweden.

Journal volume & issue: Vol. 4, no. 3
pp. 304 – 317

Abstract

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Summary: 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. Key Words: atherosclerosis, hypercholesterolemia, inflammasome, inflammation, interleukin-1

Published in JACC: Basic to Translational Science

ISSN: 2452-302X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.journals.elsevier.com/jacc-basic-to-translational-science/

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