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000305605 1001_ $$aDrekolia, Maria-Kyriaki$$b0
000305605 245__ $$aCystine import and oxidative catabolism fuel vascular growth and repair via nutrient-responsive histone acetylation.
000305605 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2026
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000305605 500__ $$aVolume 38, Issue 1, 6 January 2026, Pages 115-134.e20
000305605 520__ $$aEndothelial metabolism underpins tissue regeneration, health, and longevity. We uncover a nuclear oxidative catabolic pathway linking cystine to gene regulation. Cells preparing to proliferate upregulate the SLC7A11 transporter to import cystine, which is oxidatively catabolized by cystathionine-γ-lyase (CSE) in the nucleus. This generates acetyl units via pyruvate dehydrogenase, driving site-specific histone H3 acetylation and chromatin remodeling that sustain endothelial transcription and proliferation. Combined loss of SLC7A11 and CSE abolishes cystine oxidative and reductive metabolism and causes embryonic lethality, whereas single deletions reveal distinct effects. SLC7A11 deficiency triggers compensatory cysteine de novo biosynthesis, partially maintaining angiogenesis, while CSE deletion disrupts nuclear cystine oxidative catabolism, transcription, and vessel formation. Therapeutically, cystine supplementation promotes vascular repair in retinopathy of prematurity, myocardial infarction, and injury in aging. These findings establish the role of cystine nuclear oxidative catabolism as a fundamental metabolic axis coupling nutrient utilization to gene regulation, with implications for vascular regeneration.
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000305605 650_7 $$2Other$$aCSE
000305605 650_7 $$2Other$$aSLC7A11
000305605 650_7 $$2Other$$aaging
000305605 650_7 $$2Other$$acystine
000305605 650_7 $$2Other$$aepigenetics
000305605 650_7 $$2Other$$avascular growth
000305605 7001_ $$aMettner, Janina$$b1
000305605 7001_ $$aWang, Daiyu$$b2
000305605 7001_ $$aDelgado Lagos, Fredy$$b3
000305605 7001_ $$aKoch, Christian$$b4
000305605 7001_ $$aHecker, Dennis$$b5
000305605 7001_ $$aEresch, Jeanette$$b6
000305605 7001_ $$aMao, Yifang$$b7
000305605 7001_ $$0P:(DE-He78)cfd12c2b002e4edb674103723a470712$$aBähr, Marion$$b8$$udkfz
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000305605 7001_ $$aCordero, Julio$$b10
000305605 7001_ $$aWittig, Janina$$b11
000305605 7001_ $$aZhang, Boran$$b12
000305605 7001_ $$aCui, Hanyu$$b13
000305605 7001_ $$aLi, Xiaoming$$b14
000305605 7001_ $$aOo, James A$$b15
000305605 7001_ $$aWeigert, Andreas$$b16
000305605 7001_ $$aSiragusa, Mauro$$b17
000305605 7001_ $$aKlatt, Stephan$$b18
000305605 7001_ $$aFleming, Ingrid$$b19
000305605 7001_ $$aGünther, Stefan$$b20
000305605 7001_ $$aLooso, Mario$$b21
000305605 7001_ $$aBrandes, Ralf P$$b22
000305605 7001_ $$aLanger, Harald F$$b23
000305605 7001_ $$aPapapetropoulos, Andreas$$b24
000305605 7001_ $$aSinghal, Mahak$$b25
000305605 7001_ $$aSchulz, Marcel H$$b26
000305605 7001_ $$0P:(DE-He78)4301875630bc997edf491c694ae1f8a9$$aPlass, Christoph$$b27$$udkfz
000305605 7001_ $$aHeineke, Joerg$$b28
000305605 7001_ $$aDobreva, Gergana$$b29
000305605 7001_ $$aHu, Jiong$$b30
000305605 7001_ $$aBibli, Sofia-Iris$$b31
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