ArticleThe Journal of clinical investigation2012
Genetic inactivation of IL-1 signaling enhances atherosclerotic plaque instability and reduces outward vessel remodeling in advanced atherosclerosis in mice.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 137 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
137 citing papers in PubMed, 217 citations in OpenAlex.
- The addition of vildagliptin to metformin prevents the elevation of interleukin 1ß in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, open-label study.Cardiovascular diabetology · 2017 · on this mapTrial
- Arterial Effects of Canakinumab in Patients With Atherosclerosis and Type 2 Diabetes or Glucose Intolerance.Journal of the American College of Cardiology · 2016Trial
- Rationale and study design for a phase I/IIa trial of anakinra in children with Kawasaki disease and early coronary artery abnormalities (the ANAKID trial).Contemporary clinical trials · 2016Trial
- The Twisted Tale of Interleukin-18 in Atherosclerosis.JACC. Basic to translational science · 2026Article
- Interleukin-1 Signaling on Vascular Smooth Muscle Cells Accelerates Atherosclerosis in a Murine Model of Kawasaki Disease.Journal of the American Heart Association · 2025Article
- Review
- NLRP3 Inflammasome: A New Target for the Treatment of CVD and Depression Comorbidity.Mediators of inflammation · 2025Review
- Whys and Wherefores of Coronary Arterial Positive Remodeling.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- The Central Role of Interleukin-1 Signalling in the Pathogenesis of Kawasaki Disease Vasculitis: Path to Translation.The Canadian journal of cardiology · 2024Review
- Inflammatory crosstalk impairs phagocytic receptors and aggravates atherosclerosis in clonal hematopoiesis in mice.The Journal of clinical investigation · 2024Article
- Recent Advances in Targeted Management of Inflammation In Atherosclerosis: A Narrative Review.Cardiology and therapy · 2024Review
- The Pathological Mechanisms and Therapeutic Molecular Targets in Arteriovenous Fistula Dysfunction.International journal of molecular sciences · 2024Review
- IL-1β Inhibition Partially Negates the Beneficial Effects of Diet-Induced Atherosclerosis Regression in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Interleukin-1 receptor accessory protein blockade limits the development of atherosclerosis and reduces plaque inflammation.Cardiovascular research · 2024Article
- The role of the NLRP3 inflammasome and pyroptosis in cardiovascular diseases.Nature reviews. Cardiology · 2024Review
- "How to Release or Not Release, That Is the Question." A Review of Interleukin-1 Cellular Release Mechanisms in Vascular Inflammation.Journal of the American Heart Association · 2024Review
- Pathological and Therapeutical Implications of Pyroptosis in Psoriasis and Hidradenitis Suppurativa: A Narrative Review.Current issues in molecular biology · 2024Review
- The role of inflammasomes in human diseases and their potential as therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Thrombin-activated interleukin-1α drives atherogenesis, but also promotes vascular smooth muscle cell proliferation and collagen production.Cardiovascular research · 2023Article
- IL-1β inhibition partially negates the beneficial effects of diet-induced lipid lowering.bioRxiv : the preprint server for biology · 2023Article
77 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Clinical complications of atherosclerosis arise primarily as a result of luminal obstruction due to atherosclerotic plaque growth, with inadequate outward vessel remodeling and plaque destabilization leading to rupture. IL-1 is a proinflammatory cytokine that promotes atherogenesis in animal models, but its role in plaque destabilization and outward vessel remodeling is unclear. The studies presented herein show that advanced atherosclerotic plaques in mice lacking both IL-1 receptor type I and apolipoprotein E (Il1r1⁻/⁻Apoe⁻/⁻ mice) unexpectedly exhibited multiple features of plaque instability as compared with those of Il1r1⁺/⁺Apoe⁻/⁻ mice. These features included reduced plaque SMC content and coverage, reduced plaque collagen content, and increased intraplaque hemorrhage. In addition, the brachiocephalic arteries of Il1r1⁻/⁻Apoe⁻/⁻ mice exhibited no difference in plaque size, but reduced vessel area and lumen size relative to controls, demonstrating a reduction in outward vessel remodeling. Interestingly, expression of MMP3 was dramatically reduced within the plaque and vessel wall of Il1r1⁻/⁻Apoe⁻/⁻ mice, and Mmp3⁻/⁻Apoe⁻/⁻ mice showed defective outward vessel remodeling compared with controls. In addition, MMP3 was required for IL-1-induced SMC invasion of Matrigel in vitro. Taken together, these results show that IL-1 signaling plays a surprising dual protective role in advanced atherosclerosis by promoting outward vessel remodeling and enhancing features of plaque stability, at least in part through MMP3-dependent mechanisms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.