000255141 001__ 255141
000255141 005__ 20240112114519.0
000255141 0247_ $$2doi$$a10.1096/fj.202200056R
000255141 0247_ $$2pmid$$apmid:36794636
000255141 0247_ $$2ISSN$$a0892-6638
000255141 0247_ $$2ISSN$$a1530-6860
000255141 0247_ $$2altmetric$$aaltmetric:142662620
000255141 037__ $$aDZNE-2023-00260
000255141 041__ $$aEnglish
000255141 082__ $$a570
000255141 1001_ $$aKrammer, Christine$$b0
000255141 245__ $$aPathways linking aging and atheroprotection in Mif-deficient atherosclerotic mice.
000255141 260__ $$aHoboken, NJ$$bWiley$$c2023
000255141 3367_ $$2DRIVER$$aarticle
000255141 3367_ $$2DataCite$$aOutput Types/Journal article
000255141 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1705051942_9477
000255141 3367_ $$2BibTeX$$aARTICLE
000255141 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000255141 3367_ $$00$$2EndNote$$aJournal Article
000255141 520__ $$aAtherosclerosis is a chronic inflammatory condition of our arteries and the main underlying pathology of myocardial infarction and stroke. The pathogenesis is age-dependent, but the links between disease progression, age, and atherogenic cytokines and chemokines are incompletely understood. Here, we studied the chemokine-like inflammatory cytokine macrophage migration inhibitory factor (MIF) in atherogenic Apoe-/- mice across different stages of aging and cholesterol-rich high-fat diet (HFD). MIF promotes atherosclerosis by mediating leukocyte recruitment, lesional inflammation, and suppressing atheroprotective B cells. However, links between MIF and advanced atherosclerosis across aging have not been systematically explored. We compared effects of global Mif-gene deficiency in 30-, 42-, and 48-week-old Apoe-/- mice on HFD for 24, 36, or 42 weeks, respectively, and in 52-week-old mice on a 6-week HFD. Mif-deficient mice exhibited reduced atherosclerotic lesions in the 30/24- and 42/36-week-old groups, but atheroprotection, which in the applied Apoe-/- model was limited to lesions in the brachiocephalic artery and abdominal aorta, was not detected in the 48/42- and 52/6-week-old groups. This suggested that atheroprotection afforded by global Mif-gene deletion differs across aging stages and atherogenic diet duration. To characterize this phenotype and study the underlying mechanisms, we determined immune cells in the periphery and vascular lesions, obtained a multiplex cytokine/chemokine profile, and compared the transcriptome between the age-related phenotypes. We found that Mif deficiency promotes lesional macrophage and T-cell counts in younger but not aged mice, with subgroup analysis pointing toward a role for Trem2+ macrophages. The transcriptomic analysis identified pronounced MIF- and aging-dependent changes in pathways predominantly related to lipid synthesis and metabolism, lipid storage, and brown fat cell differentiation, as well as immunity, and atherosclerosis-relevant enriched genes such as Plin1, Ldlr, Cpne7, or Il34, hinting toward effects on lesional lipids, foamy macrophages, and immune cells. Moreover, Mif-deficient aged mice exhibited a distinct plasma cytokine/chemokine signature consistent with the notion that mediators known to drive inflamm'aging are either not downregulated or even upregulated in Mif-deficient aged mice compared with the corresponding younger ones. Lastly, Mif deficiency favored formation of lymphocyte-rich peri-adventitial leukocyte clusters. While the causative contributions of these mechanistic pillars and their interplay will be subject to future scrutiny, our study suggests that atheroprotection due to global Mif-gene deficiency in atherogenic Apoe-/- mice is reduced upon advanced aging and identifies previously unrecognized cellular and molecular targets that could explain this phenotype shift. These observations enhance our understanding of inflamm'aging and MIF pathways in atherosclerosis and may have implications for translational MIF-directed strategies.
000255141 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000255141 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000255141 650_7 $$2Other$$aMIF
000255141 650_7 $$2Other$$aaging
000255141 650_7 $$2Other$$aartery tertiary lymphoid organ
000255141 650_7 $$2Other$$aatherosclerosis
000255141 650_7 $$2Other$$aatypical chemokines
000255141 650_7 $$2Other$$achemokines
000255141 650_7 $$2NLM Chemicals$$aMacrophage Migration-Inhibitory Factors
000255141 650_7 $$2NLM Chemicals$$aChemokines
000255141 650_7 $$2NLM Chemicals$$aApolipoproteins E
000255141 650_7 $$2NLM Chemicals$$aTrem2 protein, mouse
000255141 650_7 $$2NLM Chemicals$$aMembrane Glycoproteins
000255141 650_7 $$2NLM Chemicals$$aReceptors, Immunologic
000255141 650_2 $$2MeSH$$aAnimals
000255141 650_2 $$2MeSH$$aMice
000255141 650_2 $$2MeSH$$aMacrophage Migration-Inhibitory Factors: genetics
000255141 650_2 $$2MeSH$$aMacrophage Migration-Inhibitory Factors: metabolism
000255141 650_2 $$2MeSH$$aAtherosclerosis: metabolism
000255141 650_2 $$2MeSH$$aChemokines
000255141 650_2 $$2MeSH$$aAging
000255141 650_2 $$2MeSH$$aApolipoproteins E: metabolism
000255141 650_2 $$2MeSH$$aMice, Knockout
000255141 650_2 $$2MeSH$$aMice, Inbred C57BL
000255141 650_2 $$2MeSH$$aPlaque, Atherosclerotic
000255141 650_2 $$2MeSH$$aMembrane Glycoproteins
000255141 650_2 $$2MeSH$$aReceptors, Immunologic
000255141 7001_ $$aYang, Bishan$$b1
000255141 7001_ $$aReichl, Sabrina$$b2
000255141 7001_ $$00000-0003-1194-5256$$aBesson-Girard, Simon$$b3
000255141 7001_ $$aJi, Hao$$b4
000255141 7001_ $$aBolini, Verena$$b5
000255141 7001_ $$aSchulte, Corinna$$b6
000255141 7001_ $$aNoels, Heidi$$b7
000255141 7001_ $$0P:(DE-2719)2812546$$aSchlepckow, Kai$$b8
000255141 7001_ $$0P:(DE-2719)2813355$$aJocher, Georg$$b9
000255141 7001_ $$aWerner, Georg$$b10
000255141 7001_ $$0P:(DE-HGF)0$$aWillem, Michael$$b11
000255141 7001_ $$00000-0002-3051-2096$$aEl Bounkari, Omar$$b12
000255141 7001_ $$00000-0001-6124-7232$$aKapurniotu, Aphrodite$$b13
000255141 7001_ $$0P:(DE-2719)9002754$$aGökce, Ozgun$$b14$$udzne
000255141 7001_ $$aWeber, Christian$$b15
000255141 7001_ $$00000-0001-6144-4092$$aMohanta, Sarajo$$b16
000255141 7001_ $$00000-0003-2996-2652$$aBernhagen, Jürgen$$b17
000255141 773__ $$0PERI:(DE-600)1468876-1$$a10.1096/fj.202200056R$$gVol. 37, no. 3$$n3$$pe22752$$tThe FASEB journal$$v37$$x0892-6638$$y2023
000255141 8564_ $$uhttps://pub.dzne.de/record/255141/files/DZNE-2023-00260.pdf$$yOpenAccess
000255141 8564_ $$uhttps://pub.dzne.de/record/255141/files/DZNE-2023-00260.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000255141 909CO $$ooai:pub.dzne.de:255141$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery
000255141 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812546$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b8$$kDZNE
000255141 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2813355$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b9$$kDZNE
000255141 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)9002754$$aExternal Institute$$b14$$kExtern
000255141 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0
000255141 9141_ $$y2023
000255141 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2022-11-08
000255141 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2022-11-08
000255141 915__ $$0LIC:(DE-HGF)CCBYNC4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial CC BY-NC 4.0
000255141 915__ $$0StatID:(DE-HGF)3001$$2StatID$$aDEAL Wiley$$d2022-11-08$$wger
000255141 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2022-11-08
000255141 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000255141 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bFASEB J : 2022$$d2023-10-21
000255141 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-10-21
000255141 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-10-21
000255141 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-10-21
000255141 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2023-10-21
000255141 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2023-10-21
000255141 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-10-21
000255141 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-10-21
000255141 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-10-21
000255141 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2023-10-21
000255141 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5$$d2023-10-21
000255141 9201_ $$0I:(DE-2719)1110007$$kAG Haass$$lMolecular Neurodegeneration$$x0
000255141 9201_ $$0I:(DE-2719)1110006$$kAG Lichtenthaler$$lNeuroproteomics$$x1
000255141 980__ $$ajournal
000255141 980__ $$aVDB
000255141 980__ $$aI:(DE-2719)1110007
000255141 980__ $$aI:(DE-2719)1110006
000255141 980__ $$aUNRESTRICTED
000255141 9801_ $$aFullTexts