ArticleThe Journal of clinical investigation2023
Itaconate suppresses atherosclerosis by activating a Nrf2-dependent antiinflammatory response in macrophages in mice.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 71 citations in OpenAlex.
- Roles of inflammation and metabolic dysfunction in cardiovascular diseases: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Nrf2 deficiency in myeloid cells accelerates atherosclerosis by promoting the inflammatory response and impairing efferocytosis.Journal of advanced research · 2026Article
- Intercellular transfer of LncRNABiochemistry and biophysics reports · 2026Article
- 4-octyl itaconate alleviates LPS-induced inflammation in Sertoli cells by inhibiting excessive autophagy.Redox biology · 2026Article
- Metabolite and nutrient regulation of macrophages in obesity and metabolic disease.Nature reviews. Immunology · 2026Review
- Inflammation in atherosclerosis: Drivers, mechanisms and therapies.Acta pharmaceutica Sinica. B · 2026Review
- Immunoresponsive Gene 1-Itaconate Exacerbates Hypertension by Inhibiting the Cystathionine Gamma-Lyase/Hydrogen Sulfide Pathway.Journal of cardiovascular development and disease · 2026Article
- Nrf2 signaling pathway and its molecular regulatory mechanism.Journal of Zhejiang University. Science. B · 2026Review
- Effects of intra-articular injection of dimethyl itaconate combined with systemic vancomycin on periprosthetic joint infection in rats.Bone & joint research · 2026Article
- Mitochondrial homeostasis: the central hub governing the progression of atherosclerosis.Precision clinical medicine · 2026Review
- Esculeoside A attenuates aortic remodeling and early atherosclerosis-like changes, with protective effects strongly associated with Nrf2 activation in high-cholesterol-fed rats.Scientific reports · 2026Article
- Stromal cell-derived itaconate promotes endometriosis via macrophage NRF2 and lysosomal pH modulation.Redox biology · 2026Article
- ACOD1-itaconate in macrophage attenuates oxidative stress and inflammation in benign airway stenosis by upregulating and transferring FTH1.Redox biology · 2026Article
- Estrogen deprivation induces hepatic inflammation, Indoleamine-2,3-dioxygenase 1, tryptophan catabolism, and plasma cholesterol.Scientific reports · 2026Article
- Dual itaconate delivery systems modulate macrophage Acod1-Hif-1α-glycolysis axis for immunotherapy of bioprosthetic heart valve calcification.Bioactive materials · 2026Article
- Human pneumovirus induces IFN-dependent expression of the immune-responsive gene 1 and is inhibited by 4-octyl itaconate in human macrophages.NAR molecular medicine · 2026Article
- Acod1/itaconate axis controls anxiety-like behaviors induced by chronic infection of Toxoplasma gondii in mice.PLoS neglected tropical diseases · 2026Article
- Sex-based multiomics analysis uncovers metabolic and molecular mediators linking MASH and atherosclerosis.JHEP reports : innovation in hepatology · 2026Article
- Itaconate-based nanoparticles induce immunometabolic reprogramming in macrophages and alleviate diet-induced obesity.Research square · 2026Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Itaconate has emerged as a critical immunoregulatory metabolite. Here, we examined the therapeutic potential of itaconate in atherosclerosis. We found that both itaconate and the enzyme that synthesizes it, aconitate decarboxylase 1 (Acod1, also known as immune-responsive gene 1 [IRG1]), are upregulated during atherogenesis in mice. Deletion of Acod1 in myeloid cells exacerbated inflammation and atherosclerosis in vivo and resulted in an elevated frequency of a specific subset of M1-polarized proinflammatory macrophages in the atherosclerotic aorta. Importantly, Acod1 levels were inversely correlated with clinical occlusion in atherosclerotic human aorta specimens. Treating mice with the itaconate derivative 4-octyl itaconate attenuated inflammation and atherosclerosis induced by high cholesterol. Mechanistically, we found that the antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), was required for itaconate to suppress macrophage activation induced by oxidized lipids in vitro and to decrease atherosclerotic lesion areas in vivo. Overall, our work shows that itaconate suppresses atherogenesis by inducing Nrf2-dependent inhibition of proinflammatory responses in macrophages. Activation of the itaconate pathway may represent an important approach to treat atherosclerosis.
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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.