The DOI matches its Crossref record; 147 of the 148 references it cites were found in a registry or an index.
Anticytokine Agents: Targeting Interleukin Signaling Pathways for the Treatment of Atherothrombosis
Open accessAbstract
The recognition that atherosclerosis is a complex chronic inflammatory disorder mediated through both adaptive and innate immunity has led to the hypothesis that anticytokine therapies targeting specific IL (interleukin) signaling pathways could serve as powerful adjuncts to lipid lowering in the prevention and treatment of cardiovascular disease. Cytokines involved in human atherosclerosis can be broadly classified as proinflammatory and proatherogenic (such as IL-1, IL-6, and TNF [tumor necrosis factor]) or as anti-inflammatory and antiatherogenic (such as IL-10 and IL-1rA). The recent CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) has shown that specific targeting of IL-1β can significantly reduce cardiovascular event rates without lipid or blood pressure lowering. In CANTOS, the magnitude of benefit of this cytokine-targeted approach to atherosclerosis treatment was associated to the magnitude of reduction of the central signaling cytokine IL-6 and the downstream clinical biomarker high-sensitivity CRP (C-reactive protein). By contrast, in the recent CIRT (Cardiovascular Inflammation Reduction Trial), low-dose methotrexate neither reduced IL-1β, IL-6, or high-sensitivity CRP nor lowered cardiovascular event rates. Taken together, these 2 contemporary trials provide proof of principle that focused cytokine inhibition, not broad-spectrum anti-inflammatory therapy, is likely to be crucial for atheroprotection. This review provides an overview of cytokines in atherosclerosis, the potential benefits and risks associated with targeted anticytokine therapies, and a look to the future of clinical practices addressing residual inflammatory risk.
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“particularly inhibition of the central interleukin-1β to interleukin-6 to C-reactive protein pathway of innate immunity that is important for atherosclerosis development 4,5”
From Effects of Randomized Treatment With Icosapent Ethyl and a Mineral Oil Comparator on Interleukin-1β, Interleukin-6, C-Reactive Protein, Oxidized Low-Density Lipoprotein Cholesterol, Homocysteine, Lipoprotein(a), and Lipoprotein-Associated Phospholipase A2: A REDUCE-IT Biomarker Substudy (2022) · cites this paper as [5]
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Immunity, Inflammation, and Cancer
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Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Ridker, P. M., Everett, B. M., Thuren, T., MacFadyen, J. G., Chang, W. H., Ballantyne, C., Fonseca, F., Nicolau, J., Koenig, W., Anker, S. D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1707914 · Cited by 9,482 · cited 8×
“subcutaneous canakinumab given every 3 months (50, 150, or 300 mg).(4) Virtually, all participants were on statin ther-”
BackgroundMethodResultInfluentialSelf-citationInflammation, Atherosclerosis, and Coronary Artery Disease
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Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein
Ridker, P. M., Danielson, E., Fonseca, F. A. H., Genest, J., Gotto, A. M., Kastelein, J. J. P., Koenig, W., Libby, P., Lorenzatti, A. J., MacFadyen, J. G., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0807646 · Cited by 6,674 · cited 6×
“This insight eventually led to the JUPITER trial that demonstrated considerable efficacy of high-intensity statin therapy among individuals with low levels of LDL-C but elevated levels of hsCRP.(50)”
BackgroundInfluentialSelf-citationEvolocumab and Clinical Outcomes in Patients with Cardiovascular Disease
Sabatine, M. S., Giugliano, R. P., Keech, A. C., Honarpour, N., Wiviott, S. D., Murphy, S. A., Kuder, J. F., Wang, H., Liu, T., Wasserman, S. M., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1615664 · Cited by 6,138
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“Beyond IL-1: the NLRP3 Inflammasome, IL-18, IL-6, CD40-CD40L, and TREM-1 as Alternative Cytokine Targets As critical components of the innate immune system, inflammasomes comprise macromolecular protein complexes capable of recognizing a variety of immune stimuli, including microbial and nonmicrobial pathogens, exogen…”
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Self-citationInflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men
Ridker, P. M., Cushman, M., Stampfer, M. J., Tracy, R. P., & Hennekens, C. H. (1997) · New England Journal of Medicine · doi:10.1056/nejm199704033361401 · Cited by 5,504
Self-citationAge-related clonal hematopoiesis associated with adverse outcomes
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Research works printed but not linked: 1
- Svennson, EC, Madar, A, Campbell, CD, He, Y, Sultan, M, Healey, ML, D’Aco, K, Fernandez, A, Wache-Mainier, C, Ridker, PM, Beste, MT, Basson, CT. TET-2-driven clonal hematopoiesis predicts response to canakinumab in the CANTOS trials: an exploratory analysis. Abstract presented at American Heart Association Scientific Session, November 12, 2018.
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Ridker, P. M., Devalaraja, M., Baeres, F. M. M., Engelmann, M. D. M., Hovingh, G. K., Ivkovic, M., Lo, L., Kling, D. F., Pérgola, P. E., Raj, D. S., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00520-1 · Cited by 802
Self-citationInterleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease
Ridker, P. M., & Rane, M. A. (2021) · Circulation Research · doi:10.1161/circresaha.121.319077 · Cited by 743
Self-citationTargeting cardiovascular inflammation: next steps in clinical translation
Lawler, P. R., Bhatt, D. L., Godoy, L. C., Lüscher, T. F., Bonow, R. O., Verma, S., & Ridker, P. M. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa099 · Cited by 463
Self-citationTherapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed?
Engelen, S. E., Robinson, A., Zurke, Y.-X., & Monaco, C. G. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00668-4 · Cited by 455
Dziedzic, E. A., Gąsior, J. S., Tuzimek, A., Paleczny, J., Junka, A., Dąbrowski, M., & Jankowski, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179553 · Cited by 345
Metadata
- Authors
- Ridker, P. M.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Ridker, Paul M
- ORCID
- Ridker, Paul M
- Venue
- Circulation Research
- Published
- 2019-02
- Volume
- 124
- Issue
- 3
- Pages
- 437-450
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC6386195
- OpenAlex
- W2914237180
- Cited by
- 260
- References
- 148
- Citations by year
- 2026: 15 · 2025: 30 · 2024: 30 · 2023: 38 · 2022: 42 · 2021: 40 · 2020: 37 · 2019: 28
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (U01HL101422)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- anti-cytokine therapy, atherosclerosis, cytokines, IL-1β, interleukin-6, TNF-α, CANTOS trial, methotrexate, cardiovascular inflammation, high-sensitivity C-reactive protein, residual inflammatory risk, atheroprotection, cardiovascular disease prevention
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Triggering Receptor Expressed on Myeloid Cells-1, Interleukin-6 Inhibitors, Animals, Antibodies, Monoclonal, C-Reactive Protein, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Disease Models, Animal, Hematopoiesis, Humans, Methotrexate, Thrombosis, Signal Transduction, Randomized Controlled Trials as Topic, CD40 Antigens, Interleukin-18, Stroke, CD40 Ligand, Atherosclerosis, Mice, Renal Insufficiency, Chronic, Interleukin-1beta, Inflammasomes, Antibodies, Monoclonal, Humanized
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