| Autor: |
Karl J. Harber, Annette E. Neele, Cindy PAA. van Roomen, Marion JJ. Gijbels, Linda Beckers, Myrthe den Toom, Bauke V. Schomakers, Daan AF. Heister, Lisa Willemsen, Guillermo R. Griffith, Kyra E. de Goede, Xanthe AMH. van Dierendonck, Myrthe E. Reiche, Aurélie Poli, Frida L-H Mogensen, Alessandro Michelucci, Sanne GS. Verberk, Helga de Vries, Michel van Weeghel, Jan Van den Bossche, Menno PJ. de Winther |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Redox Biology, Vol 70, Iss , Pp 103054- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2213-2317 |
| DOI: |
10.1016/j.redox.2024.103054 |
| Popis: |
Inflammatory macrophages are key drivers of atherosclerosis that can induce rupture-prone vulnerable plaques. Skewing the plaque macrophage population towards a more protective phenotype and reducing the occurrence of clinical events is thought to be a promising method of treating atherosclerotic patients. In the current study, we investigate the immunomodulatory properties of itaconate, an immunometabolite derived from the TCA cycle intermediate cis-aconitate and synthesised by the enzyme Aconitate Decarboxylase 1 (ACOD1, also known as IRG1), in the context of atherosclerosis. Ldlr−/− atherogenic mice transplanted with Acod1−/− bone marrow displayed a more stable plaque phenotype with smaller necrotic cores and showed increased recruitment of monocytes to the vessel intima. Macrophages from Acod1−/− mice contained more lipids whilst also displaying reduced induction of apoptosis. Using multi-omics approaches, we identify a metabolic shift towards purine metabolism, in addition to an altered glycolytic flux towards production of glycerol for triglyceride synthesis. Overall, our data highlight the potential of therapeutically blocking ACOD1 with the aim of stabilizing atherosclerotic plaques. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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