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000277434 1001_ $$00000-0002-3051-2096$$aEl Bounkari, Omar$$b0
000277434 245__ $$aAn atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis.
000277434 260__ $$a[London]$$bSpringer Nature$$c2025
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000277434 520__ $$aAtherosclerosis 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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000277434 650_7 $$0EC 5.3.-$$2NLM Chemicals$$aIntramolecular Oxidoreductases
000277434 650_7 $$2NLM Chemicals$$aChemokines
000277434 650_7 $$2NLM Chemicals$$aReceptors, CXCR4
000277434 650_7 $$0EC 5.3.3.12$$2NLM Chemicals$$adopachrome isomerase
000277434 650_7 $$2NLM Chemicals$$aMacrophage Migration-Inhibitory Factors
000277434 650_7 $$2NLM Chemicals$$aCXCR4 protein, mouse
000277434 650_2 $$2MeSH$$aAnimals
000277434 650_2 $$2MeSH$$aLipogenesis: genetics
000277434 650_2 $$2MeSH$$aAtherosclerosis: metabolism
000277434 650_2 $$2MeSH$$aAtherosclerosis: pathology
000277434 650_2 $$2MeSH$$aAtherosclerosis: genetics
000277434 650_2 $$2MeSH$$aHumans
000277434 650_2 $$2MeSH$$aMice
000277434 650_2 $$2MeSH$$aLiver: metabolism
000277434 650_2 $$2MeSH$$aLiver: pathology
000277434 650_2 $$2MeSH$$aIntramolecular Oxidoreductases: metabolism
000277434 650_2 $$2MeSH$$aIntramolecular Oxidoreductases: genetics
000277434 650_2 $$2MeSH$$aMale
000277434 650_2 $$2MeSH$$aChemokines: metabolism
000277434 650_2 $$2MeSH$$aReceptors, CXCR4: metabolism
000277434 650_2 $$2MeSH$$aReceptors, CXCR4: genetics
000277434 650_2 $$2MeSH$$aMice, Inbred C57BL
000277434 650_2 $$2MeSH$$aHepatocytes: metabolism
000277434 650_2 $$2MeSH$$aHepatocytes: pathology
000277434 650_2 $$2MeSH$$aMacrophage Migration-Inhibitory Factors: metabolism
000277434 650_2 $$2MeSH$$aMacrophage Migration-Inhibitory Factors: genetics
000277434 650_2 $$2MeSH$$aMice, Knockout
000277434 650_2 $$2MeSH$$aFemale
000277434 650_2 $$2MeSH$$aSignal Transduction
000277434 650_2 $$2MeSH$$aFoam Cells: metabolism
000277434 7001_ $$aZan, Chunfang$$b1
000277434 7001_ $$aYang, Bishan$$b2
000277434 7001_ $$0P:(DE-2719)9002651$$aEbert, Simon$$b3$$udzne
000277434 7001_ $$aWagner, Jonas$$b4
000277434 7001_ $$aBugar, Elina$$b5
000277434 7001_ $$aKramer, Naomi$$b6
000277434 7001_ $$aBourilhon, Priscila$$b7
000277434 7001_ $$aKontos, Christos$$b8
000277434 7001_ $$aZarwel, Marlies$$b9
000277434 7001_ $$aSinitski, Dzmitry$$b10
000277434 7001_ $$aMilic, Jelena$$b11
000277434 7001_ $$aJansen, Yvonne$$b12
000277434 7001_ $$aKempf, Wolfgang E$$b13
000277434 7001_ $$00000-0001-8031-017X$$aSachs, Nadja$$b14
000277434 7001_ $$00000-0001-5228-2634$$aMaegdefessel, Lars$$b15
000277434 7001_ $$aJi, Hao$$b16
000277434 7001_ $$0P:(DE-2719)9002754$$aGokce, Ozgun$$b17$$udzne
000277434 7001_ $$aRiols, Fabien$$b18
000277434 7001_ $$00000-0001-6118-1333$$aHaid, Mark$$b19
000277434 7001_ $$aGerra, Simona$$b20
000277434 7001_ $$00009-0000-0661-2321$$aHoffmann, Adrian$$b21
000277434 7001_ $$00000-0002-1629-8353$$aBrandhofer, Markus$$b22
000277434 7001_ $$aAvdic, Maida$$b23
000277434 7001_ $$aBucala, Richard$$b24
000277434 7001_ $$00000-0001-9871-6696$$aMegens, Remco T A$$b25
000277434 7001_ $$aWillemsen, Nienke$$b26
000277434 7001_ $$aMesserer, Denise$$b27
000277434 7001_ $$00000-0002-8149-0747$$aSchulz, Christian$$b28
000277434 7001_ $$00000-0001-7840-3991$$aBartelt, Alexander$$b29
000277434 7001_ $$aHarm, Tobias$$b30
000277434 7001_ $$aRath, Dominik$$b31
000277434 7001_ $$00000-0001-9307-3396$$aDöring, Yvonne$$b32
000277434 7001_ $$00000-0003-1124-9592$$aGawaz, Meinrad$$b33
000277434 7001_ $$aWeber, Christian$$b34
000277434 7001_ $$aKapurniotu, Aphrodite$$b35
000277434 7001_ $$00000-0003-2996-2652$$aBernhagen, Jürgen$$b36
000277434 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-57540-z$$gVol. 16, no. 1, p. 2297$$n1$$p2297$$tNature Communications$$v16$$x2041-1723$$y2025
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