000285050 001__ 285050
000285050 005__ 20260209105649.0
000285050 0247_ $$2doi$$a10.1038/s41593-025-02136-5
000285050 0247_ $$2pmid$$apmid:41398477
000285050 0247_ $$2pmc$$apmc:PMC12880920
000285050 0247_ $$2ISSN$$a1097-6256
000285050 0247_ $$2ISSN$$a1546-1726
000285050 037__ $$aDZNE-2026-00174
000285050 041__ $$aEnglish
000285050 082__ $$a610
000285050 1001_ $$00009-0007-8073-9524$$aTodorov-Völgyi, Katalin$$b0
000285050 245__ $$aThe stroke risk gene Foxf2 maintains brain endothelial cell function via Tie2 signaling.
000285050 260__ $$aNew York, NY$$bNature America$$c2026
000285050 3367_ $$2DRIVER$$aarticle
000285050 3367_ $$2DataCite$$aOutput Types/Journal article
000285050 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1770630750_24271
000285050 3367_ $$2BibTeX$$aARTICLE
000285050 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000285050 3367_ $$00$$2EndNote$$aJournal Article
000285050 520__ $$aCerebral small vessel disease (SVD) is a common chronic cerebrovascular disorder with poorly understood pathomechanisms. Genetic studies have identified FOXF2 as a major risk gene for both SVD and stroke. FOXF2 encodes a transcription factor primarily expressed in brain pericytes and endothelial cells (ECs); however, its mechanistic role in cerebrovascular disease remains unknown. Here we show that Foxf2 maintains EC function through Tie2 signaling. RNA and chromatin sequencing identified FOXF2 as a transcriptional activator of Tie2 and other endothelial lineage-specific genes. The deletion of EC-specific Foxf2 in adult mice resulted in blood-brain barrier leakage, which worsened after experimental stroke. Proteomic analyses of Foxf2-deficient mouse brain-derived and human-induced pluripotent stem cell-derived ECs that lack FOXF2 revealed a downregulation of multiple proteins involved in Tie2 signaling. Endothelial Foxf2 deficiency impaired functional hyperemia, reduced NO production and increased infarct size through disrupted Tie2 signaling, effects that were rescued by pharmacological activation of Tie2 with AKB-9778. Collectively, our results highlight the critical role of Foxf2-regulated Tie2 signaling in SVD and stroke, suggesting new avenues for therapeutic interventions.
000285050 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0
000285050 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x1
000285050 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x2
000285050 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000285050 650_7 $$2NLM Chemicals$$aForkhead Transcription Factors
000285050 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aReceptor, TIE-2
000285050 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aTek protein, mouse
000285050 650_7 $$2NLM Chemicals$$aFoxf2 protein, mouse
000285050 650_2 $$2MeSH$$aAnimals
000285050 650_2 $$2MeSH$$aForkhead Transcription Factors: genetics
000285050 650_2 $$2MeSH$$aForkhead Transcription Factors: metabolism
000285050 650_2 $$2MeSH$$aEndothelial Cells: metabolism
000285050 650_2 $$2MeSH$$aEndothelial Cells: physiology
000285050 650_2 $$2MeSH$$aReceptor, TIE-2: metabolism
000285050 650_2 $$2MeSH$$aReceptor, TIE-2: genetics
000285050 650_2 $$2MeSH$$aMice
000285050 650_2 $$2MeSH$$aSignal Transduction: physiology
000285050 650_2 $$2MeSH$$aSignal Transduction: genetics
000285050 650_2 $$2MeSH$$aStroke: genetics
000285050 650_2 $$2MeSH$$aStroke: metabolism
000285050 650_2 $$2MeSH$$aBrain: metabolism
000285050 650_2 $$2MeSH$$aHumans
000285050 650_2 $$2MeSH$$aBlood-Brain Barrier: metabolism
000285050 650_2 $$2MeSH$$aMice, Knockout
000285050 650_2 $$2MeSH$$aMale
000285050 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: genetics
000285050 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: metabolism
000285050 650_2 $$2MeSH$$aMice, Inbred C57BL
000285050 7001_ $$aGonzález-Gallego, Judit$$b1
000285050 7001_ $$0P:(DE-2719)2810938$$aMüller, Stephan A$$b2
000285050 7001_ $$00000-0002-8627-1260$$aTodorov, Mihail Ivilinov$$b3
000285050 7001_ $$aSeker, Fatma Burcu$$b4
000285050 7001_ $$00000-0002-8275-6113$$aFrerich, Simon$$b5
000285050 7001_ $$00000-0003-2814-3436$$aCernilogar, Filippo M$$b6
000285050 7001_ $$00000-0002-6213-4202$$aSchröger, Luise$$b7
000285050 7001_ $$aMalik, Rainer$$b8
000285050 7001_ $$00000-0002-8826-2595$$aCao, Jiayu$$b9
000285050 7001_ $$aLlovera, Gemma$$b10
000285050 7001_ $$00000-0001-6823-2981$$aRoth, Stefan$$b11
000285050 7001_ $$aSchillinger, Ulrike$$b12
000285050 7001_ $$0P:(DE-2719)2812260$$aSchifferer, Martina$$b13
000285050 7001_ $$aReyahi, Azadeh$$b14
000285050 7001_ $$aCrusius, Dennis$$b15
000285050 7001_ $$aPedro, Liliana D$$b16
000285050 7001_ $$0P:(DE-2719)2811642$$aSimons, Mikael$$b17
000285050 7001_ $$aCarlsson, Peter$$b18
000285050 7001_ $$aErtürk, Ali$$b19
000285050 7001_ $$00000-0002-9069-2594$$aLiesz, Arthur$$b20
000285050 7001_ $$00000-0003-4940-6135$$aSchotta, Gunnar$$b21
000285050 7001_ $$0P:(DE-2719)9000853$$aPlesnila, Nikolaus$$b22
000285050 7001_ $$0P:(DE-2719)2181459$$aLichtenthaler, Stefan F$$b23$$udzne
000285050 7001_ $$0P:(DE-2719)2010112$$aPaquet, Dominik$$b24
000285050 7001_ $$0P:(DE-2719)2000030$$aDichgans, Martin$$b25$$eLast author
000285050 773__ $$0PERI:(DE-600)1494955-6$$a10.1038/s41593-025-02136-5$$gVol. 29, no. 2, p. 325 - 336$$n2$$p325 - 336$$tNature neuroscience$$v29$$x1097-6256$$y2026
000285050 8564_ $$uhttps://pub.dzne.de/record/285050/files/DZNE-2026-00174.pdf$$yRestricted
000285050 8564_ $$uhttps://pub.dzne.de/record/285050/files/DZNE-2026-00174.pdf?subformat=pdfa$$xpdfa$$yRestricted
000285050 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810938$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE
000285050 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812260$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b13$$kDZNE
000285050 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811642$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b17$$kDZNE
000285050 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2181459$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b23$$kDZNE
000285050 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2000030$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b25$$kDZNE
000285050 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x0
000285050 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$$vDisease Mechanisms$$x1
000285050 9131_ $$0G:(DE-HGF)POF4-351$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vBrain Function$$x2
000285050 915__ $$0StatID:(DE-HGF)0430$$2StatID$$aNational-Konsortium$$d2025-11-07$$wger
000285050 915__ $$0StatID:(DE-HGF)3003$$2StatID$$aDEAL Nature$$d2025-11-07$$wger
000285050 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2025-11-07
000285050 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2025-11-07
000285050 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2025-11-07
000285050 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2025-11-07
000285050 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2025-11-07
000285050 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2025-11-07
000285050 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2025-11-07
000285050 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2025-11-07
000285050 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2025-11-07
000285050 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNAT NEUROSCI : 2022$$d2025-11-07
000285050 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2025-11-07
000285050 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2025-11-07
000285050 915__ $$0StatID:(DE-HGF)9925$$2StatID$$aIF >= 25$$bNAT NEUROSCI : 2022$$d2025-11-07
000285050 9201_ $$0I:(DE-2719)5000022$$kAG Dichgans$$lVascular Cognitive Impairment & Post-Stroke Dementia$$x0
000285050 9201_ $$0I:(DE-2719)1110006$$kAG Lichtenthaler$$lNeuroproteomics$$x1
000285050 9201_ $$0I:(DE-2719)1110000-4$$kAG Misgeld$$lNeuronal Cell Biology$$x2
000285050 9201_ $$0I:(DE-2719)1110008$$kAG Simons$$lMolecular Neurobiology$$x3
000285050 980__ $$ajournal
000285050 980__ $$aEDITORS
000285050 980__ $$aVDBINPRINT
000285050 980__ $$aI:(DE-2719)5000022
000285050 980__ $$aI:(DE-2719)1110006
000285050 980__ $$aI:(DE-2719)1110000-4
000285050 980__ $$aI:(DE-2719)1110008
000285050 980__ $$aUNRESTRICTED