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Inflammasome-Driven Interleukin-1α and Interleukin-1β Production in Atherosclerotic Plaques Relates to Hyperlipidemia and Plaque Complexity.
JACC Basic Transl Sci 2019; 4(3):304-317JB

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31312755

Citation

Jiang, Xintong, et al. "Inflammasome-Driven Interleukin-1α and Interleukin-1β Production in Atherosclerotic Plaques Relates to Hyperlipidemia and Plaque Complexity." JACC. Basic to Translational Science, vol. 4, no. 3, 2019, pp. 304-317.
Jiang X, Wang F, Wang Y, et al. Inflammasome-Driven Interleukin-1α and Interleukin-1β Production in Atherosclerotic Plaques Relates to Hyperlipidemia and Plaque Complexity. JACC Basic Transl Sci. 2019;4(3):304-317.
Jiang, X., Wang, F., Wang, Y., Gisterå, A., Roy, J., Paulsson-Berne, G., ... Yan, Z. Q. (2019). Inflammasome-Driven Interleukin-1α and Interleukin-1β Production in Atherosclerotic Plaques Relates to Hyperlipidemia and Plaque Complexity. JACC. Basic to Translational Science, 4(3), pp. 304-317. doi:10.1016/j.jacbts.2019.02.007.
Jiang X, et al. Inflammasome-Driven Interleukin-1α and Interleukin-1β Production in Atherosclerotic Plaques Relates to Hyperlipidemia and Plaque Complexity. JACC Basic Transl Sci. 2019;4(3):304-317. PubMed PMID: 31312755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inflammasome-Driven Interleukin-1α and Interleukin-1β Production in Atherosclerotic Plaques Relates to Hyperlipidemia and Plaque Complexity. AU - Jiang,Xintong, AU - Wang,Feilong, AU - Wang,Yajuan, AU - Gisterå,Anton, AU - Roy,Joy, AU - Paulsson-Berne,Gabrielle, AU - Hedin,Ulf, AU - Lerman,Amir, AU - Hansson,Göran K, AU - Herrmann,Joerg, AU - Yan,Zhong-Qun, Y1 - 2019/06/24/ PY - 2018/10/09/received PY - 2018/11/24/revised PY - 2019/02/11/accepted PY - 2019/7/18/entrez PY - 2019/7/18/pubmed PY - 2019/7/18/medline KW - ASC, apoptosis-associated speck-like protein containing a CARD KW - ATP, adenosine 5′-triphosphate disodium salt hydrate KW - BiKE, Biobank of Karolinska Carotid Endarterectomies KW - CT, Computerized tomographic scanning KW - IL, interleukin KW - LDL, low-density lipoprotein KW - LPS, lipopolysaccharide KW - NLRC, nucleotide-binding oligomerization domain, leucine-rich repeat and CARD domain–containing protein KW - NLRP, nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain–containing protein KW - PBS, phosphate-buffered saline KW - atherosclerosis KW - hypercholesterolemia KW - inflammasome KW - inflammation KW - interleukin-1 KW - mRNA, messenger ribonucleic acid SP - 304 EP - 317 JF - JACC. Basic to translational science JO - JACC Basic Transl Sci VL - 4 IS - 3 N2 - 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. SN - 2452-302X UR - https://www.unboundmedicine.com/medline/citation/31312755/Inflammasome-Driven_Interleukin-1α_and_Interleukin-1β_Production_in_Atherosclerotic_Plaques_Relates_to_Hyperlipidemia_and_Plaque_Complexity L2 - https://linkinghub.elsevier.com/retrieve/pii/S2452-302X(19)30068-3 DB - PRIME DP - Unbound Medicine ER -