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. 2025 Jun 12;135(15):e182472.
doi: 10.1172/JCI182472. eCollection 2025 Aug 1.

Modulation of the ACOD1/itaconate pathway differentially affects atherosclerosis severity across genetic models and sexes

Affiliations

Modulation of the ACOD1/itaconate pathway differentially affects atherosclerosis severity across genetic models and sexes

Lara Haase et al. J Clin Invest. .
No abstract available

Keywords: Atherosclerosis; Cardiology; Macrophages; Vascular biology.

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Figures

Figure 1
Figure 1. Acod1 deletion has no effect on atherosclerosis but shows sex-dependent cholesterol metabolism in the Ldlr model.
Ldlr–/–Acod1–/– and control Ldlr–/– mice (6–12 weeks old) were fed a Western diet (Envigo, TD-88137) for 12 weeks. Plaque area was measured in the aortic root (A, n = 7–8/sex/group), thoracic/abdominal aorta (C, males n = 9–16, females n = 12–14), and aortic arch (D, n = 7–8/sex/group). Representative aortic arch images from females are shown (B and E). Circulating T cells were analyzed by flow cytometry (F, males n = 10–16, females n = 12–14, pooled right), gated as CD45+TCRβ+CD19 cells. Shown are representative dot plots (G). Weight gain (H, males n = 11–16, females n = 14–15), plasma cholesterol (I, n = 8–11/group), and liver IL-1β levels (J, n = 8–10/group, pooled right) were quantified. Data are shown as mean ± SD. *P < 0.05; ***P < 0.001 by Mann-Whitney U test (A, C, and D) or Welch’s t test (FJ). Scale bars: 300 μm (B) and 1 mm (E).

Comment on

  • Itaconate suppresses atherosclerosis by activating a Nrf2-dependent antiinflammatory response in macrophages in mice

References

    1. Mills EL, et al. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature. 2018;556(7699):113–117. doi: 10.1038/nature25986. - DOI - PMC - PubMed
    1. Swain A, et al. Comparative evaluation of itaconate and its derivatives reveals divergent inflammasome and type I interferon regulation in macrophages. Nat Metab. 2020;2(7):594–602. doi: 10.1038/s42255-020-0210-0. - DOI - PMC - PubMed
    1. Song J, et al. Itaconate suppresses atherosclerosis by activating a Nrf2-dependent anti-inflammatory response in macrophages in mice. J Clin Invest. 2024;134(3):e173034. doi: 10.1172/JCI173034. - DOI - PMC - PubMed
    1. Harber KJ, et al. Targeting the ACOD1-itaconate axis stabilizes atherosclerotic plaques. Redox Biol. 2024;70:103054. doi: 10.1016/j.redox.2024.103054. - DOI - PMC - PubMed
    1. Weiss JM, et al. Itaconic acid underpins hepatocyte lipid metabolism in non-alcoholic fatty liver disease in male mice. Nat Metab. 2023;5(6):981–995. doi: 10.1038/s42255-023-00801-2. - DOI - PMC - PubMed