TY  - JOUR
A1  - Bibli, Sofia Iris
A1  - Hu, Jiong
A1  - Leisegang, Matthias
A1  - Wittig, Janina
A1  - Zukunft, Sven
A1  - Kapasakalidi, Andrea
A1  - Fißlthaler, Beate
A1  - Tsilimigras, Diamantis I.
A1  - Zografos, Georgios
A1  - Filis, Konstantinos
A1  - Brandes, Ralf
A1  - Papapetropoulos, Andreas
A1  - Sigala, Fragiska
A1  - Fleming, Ingrid
T1  - Shear stress regulates cystathionine γ lyase expression to preserve endothelial redox balance and reduce membrane lipid peroxidation
T2  - Redox Biology
N2  - Cystathionine γ lyase (CSE) is the major source of hydrogen sulfide-derived species (H2Sn) in endothelial cells and plays an important role in protecting against atherosclerosis. Here we investigated the molecular mechanisms underlying the regulation of CSE expression in endothelial cells by fluid shear stress/flow. Fluid shear stress decreased CSE expression in human and murine endothelial cells and was negatively correlated with the transcription factor Krüppel-like factor (KLF) 2. CSE was identified as a direct target of the KLF2-regulated microRNA, miR-27b and high expression of CSE in native human plaque-derived endothelial cells, was also inversely correlated with KLF2 and miR-27b levels. One consequence of decreased CSE expression was the loss of Prx6 sulfhydration (on Cys47), which resulted in Prx6 hyperoxidation, decamerization and inhibition, as well as a concomitant increase in endothelial cell reactive oxygen species and lipid membrane peroxidation. H2Sn supplementation in vitro was able to reverse the redox state of Prx6. Statin therapy, which is known to activate KLF2, also decreased CSE expression but increased CSE activity by preventing its phosphorylation on Ser377. As a result, the sulfhydration of Prx6 was partially restored in samples from plaque containing arteries from statin-treated donors. Taken together, the regulation of CSE expression by shear stress/disturbed flow is dependent on KLF2 and miR-27b. Moreover, in murine and human arteries CSE acts to maintain endothelial redox balance at least partly by targeting Prx6 to prevent its decamerization and inhibition of its peroxidase activity.
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51821
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-518215
SN  - 2213-2317
N1  - © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
VL  - 28
IS  - Art. 101379
SP  - 1
EP  - 10
PB  - Elsevier
CY  - Amsterdam [u. a.]
ER  -