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024 7 _ |a 10.1038/s41467-025-57540-z
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037 _ _ |a DZNE-2025-00417
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a El Bounkari, Omar
|0 0000-0002-3051-2096
|b 0
245 _ _ |a An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis.
260 _ _ |a [London]
|c 2025
|b Springer Nature
336 7 _ |a article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Atherosclerosis is the underlying cause of myocardial infarction and ischemic stroke. It is a lipid-triggered and cytokine/chemokine-driven arterial inflammatory condition. We identify D-dopachrome tautomerase/macrophage migration-inhibitory factor-2 (MIF-2), a paralog of the cytokine MIF, as an atypical chemokine promoting both atherosclerosis and hepatic lipid accumulation. In hyperlipidemic Apoe-/- mice, Mif-2-deficiency and pharmacological MIF-2-blockade protect against lesion formation and vascular inflammation in early and advanced atherogenesis. MIF-2 promotes leukocyte migration, endothelial arrest, and foam-cell formation, and we identify CXCR4 as a receptor for MIF-2. Mif-2-deficiency in Apoe-/- mice leads to decreased plasma lipid levels and suppressed hepatic lipid accumulation, characterized by reductions in lipogenesis-related pathways, tri-/diacylglycerides, and cholesterol-esters, as revealed by hepatic transcriptomics/lipidomics. Hepatocyte cultures and FLIM-FRET-microscopy suggest that MIF-2 activates SREBP-driven lipogenic genes, mechanistically involving MIF-2-inducible CD74/CXCR4 complexes and PI3K/AKT but not AMPK signaling. MIF-2 is upregulated in unstable carotid plaques from atherosclerotic patients and its plasma concentration correlates with disease severity in patients with coronary artery disease. These findings establish MIF-2 as an atypical chemokine linking vascular inflammation to metabolic dysfunction in atherosclerosis.
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650 _ 7 |a Intramolecular Oxidoreductases
|0 EC 5.3.-
|2 NLM Chemicals
650 _ 7 |a Chemokines
|2 NLM Chemicals
650 _ 7 |a Receptors, CXCR4
|2 NLM Chemicals
650 _ 7 |a dopachrome isomerase
|0 EC 5.3.3.12
|2 NLM Chemicals
650 _ 7 |a Macrophage Migration-Inhibitory Factors
|2 NLM Chemicals
650 _ 7 |a CXCR4 protein, mouse
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Lipogenesis: genetics
|2 MeSH
650 _ 2 |a Atherosclerosis: metabolism
|2 MeSH
650 _ 2 |a Atherosclerosis: pathology
|2 MeSH
650 _ 2 |a Atherosclerosis: genetics
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Liver: metabolism
|2 MeSH
650 _ 2 |a Liver: pathology
|2 MeSH
650 _ 2 |a Intramolecular Oxidoreductases: metabolism
|2 MeSH
650 _ 2 |a Intramolecular Oxidoreductases: genetics
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Chemokines: metabolism
|2 MeSH
650 _ 2 |a Receptors, CXCR4: metabolism
|2 MeSH
650 _ 2 |a Receptors, CXCR4: genetics
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Hepatocytes: metabolism
|2 MeSH
650 _ 2 |a Hepatocytes: pathology
|2 MeSH
650 _ 2 |a Macrophage Migration-Inhibitory Factors: metabolism
|2 MeSH
650 _ 2 |a Macrophage Migration-Inhibitory Factors: genetics
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Signal Transduction
|2 MeSH
650 _ 2 |a Foam Cells: metabolism
|2 MeSH
700 1 _ |a Zan, Chunfang
|b 1
700 1 _ |a Yang, Bishan
|b 2
700 1 _ |a Ebert, Simon
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700 1 _ |a Wagner, Jonas
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700 1 _ |a Bugar, Elina
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700 1 _ |a Kramer, Naomi
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700 1 _ |a Bourilhon, Priscila
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700 1 _ |a Kontos, Christos
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700 1 _ |a Zarwel, Marlies
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700 1 _ |a Sinitski, Dzmitry
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700 1 _ |a Milic, Jelena
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700 1 _ |a Jansen, Yvonne
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700 1 _ |a Kempf, Wolfgang E
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700 1 _ |a Sachs, Nadja
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700 1 _ |a Maegdefessel, Lars
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700 1 _ |a Ji, Hao
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700 1 _ |a Gokce, Ozgun
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700 1 _ |a Riols, Fabien
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700 1 _ |a Haid, Mark
|0 0000-0001-6118-1333
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700 1 _ |a Gerra, Simona
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700 1 _ |a Hoffmann, Adrian
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700 1 _ |a Brandhofer, Markus
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700 1 _ |a Avdic, Maida
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700 1 _ |a Bucala, Richard
|b 24
700 1 _ |a Megens, Remco T A
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700 1 _ |a Willemsen, Nienke
|b 26
700 1 _ |a Messerer, Denise
|b 27
700 1 _ |a Schulz, Christian
|0 0000-0002-8149-0747
|b 28
700 1 _ |a Bartelt, Alexander
|0 0000-0001-7840-3991
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700 1 _ |a Harm, Tobias
|b 30
700 1 _ |a Rath, Dominik
|b 31
700 1 _ |a Döring, Yvonne
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700 1 _ |a Gawaz, Meinrad
|0 0000-0003-1124-9592
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700 1 _ |a Weber, Christian
|b 34
700 1 _ |a Kapurniotu, Aphrodite
|b 35
700 1 _ |a Bernhagen, Jürgen
|0 0000-0003-2996-2652
|b 36
773 _ _ |a 10.1038/s41467-025-57540-z
|g Vol. 16, no. 1, p. 2297
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