ArticleProceedings of the National Academy of Sciences of the United States of America2022
Interleukin 38 alleviates aortic valve calcification by inhibition of NLRP3.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 40 citations in OpenAlex.
- KLF5 Downregulation Links Impaired BNIP3-Mediated Mitophagy to Inflammatory Valve Remodeling in Calcific Aortic Valve Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mast Cells Accumulate in the Stroma of Breast Adenocarcinoma and Secrete Pro-Inflammatory Cytokines and Tumor-Damaging Mediators: Could IL-37 and IL-38 Play an Anti-Tumor Role?International journal of molecular sciences · 2026Review
- Integrated biomarker landscape for the early detection and management of calcific aortic valve disease.European journal of clinical investigation · 2026Review
- Article
- The Pathogenic Roles of Local Vitamin D Metabolism Defect in Valve Inflammation and Calcification.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- IL-38 attenuates vascular calcification by upregulating GPX3-mediated antioxidant defense via the PPAR-γ/NRF2 axis.Cellular and molecular life sciences : CMLS · 2025Article
- Interleukin-38 is a negative regulator of trained immunity-A retrospective multi-omics study.iScience · 2025Article
- Oxidized LDL-induced FOXS1 mediates cholesterol transport dysfunction and inflammasome activation to drive aortic valve calcification.Cardiovascular research · 2025Article
- AI-based modality-agnostic classification system for vascular calcifications.Scientific reports · 2025Article
- Pharmacological targeting of the IL-17/neutrophil axis attenuates calcific deposits in rat models of calciphylaxis.The Journal of clinical investigation · 2025Article
- Navigating the Landscape of Translational Medicine of Calcific Aortic Valve Disease: Bridging Bench to Bedside.JACC. Asia · 2025Review
- Macrophages as key modulators of calcific aortic valve disease.Frontiers in cardiovascular medicine · 2025Review
- Editorial: Community series in advances in pathogenesis and therapies of gout, volume II.Frontiers in immunology · 2025Article
- Dichotomous roles of IL-36 and IL-38 in cardiovascular disease.Frontiers in immunology · 2025Review
- Insights into preclinical models of calcific aortic valve disease and their translational potential.Frontiers in cardiovascular medicine · 2025Review
- Low skeletal muscle density is independently associated with cardiac valve calcification in dialysis patients.Frontiers in physiology · 2025Article
- The association between triglyceride to high-density-lipoprotein cholesterol ratio and calcific aortic valve disease: a retrospective study.BMC cardiovascular disorders · 2024Article
- Advanced glycation end product-modified low-density lipoprotein promotes pro-osteogenic reprogramming via RAGE/NF-κB pathway and exaggerates aortic valve calcification in hamsters.Molecular medicine (Cambridge, Mass.) · 2024Article
- Empagliflozin ameliorates vascular calcification in diabetic mice through inhibiting Bhlhe40-dependent NLRP3 inflammasome activation.Acta pharmacologica Sinica · 2024Article
- Models for calcific aortic valve disease in vivo and in vitro.Cell regeneration (London, England) · 2024Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Calcific aortic valve disease (CAVD) is common in people over the age of 65. Progressive valvular calcification is a characteristic of CAVD and due to chronic inflammation in aortic valve interstitial cells (AVICs) resulting in CAVD progression. IL-38 is a naturally occurring anti-inflammatory cytokine; here, we report lower levels of endogenous IL-38 in AVICs isolated from patients' CAVD valves compared to AVICs from non-CAVD valves. Recombinant IL-38 suppressed spontaneous inflammatory activity and calcium deposition in cultured AVICs. In mice, knockdown of IL-38 enhanced the production of inflammatory mediators in murine AVICs exposed to the proinflammatory stimulant matrilin-2. We also observed that in cultured AVICs matrilin-2 stimulation activated the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome with procaspase-1 cleavage into active caspase-1. The addition of IL-38 to matrilin-2-treated AVICs suppressed caspase-1 activation and reduced the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, runt-related transcription factor 2, and alkaline phosphatase. Aged IL-38-deficient mice fed a high-fat diet exhibited aortic valve lesions compared to aged wild-type mice fed the same diet. The interleukin-1 receptor 9 (IL-1R9) is the putative receptor mediating the anti-inflammatory properties of IL-38; we observed that IL-1R9-deficient mice exhibited spontaneous aortic valve thickening and greater calcium deposition in AVICs compared to wild-type mice. These data demonstrate that IL-38 suppresses spontaneous and stimulated osteogenic activity in aortic valve via inhibition of the NLRP3 inflammasome and caspase-1. The findings of this study suggest that IL-38 has therapeutic potential for prevention of CAVD progression.
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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 Socratic graph.