TY  - JOUR
A1  - Buchmann, Giulia Karolin
A1  - Schürmann, Christoph
A1  - Spaeth, Manuela
A1  - Abplanalp, Wesley
A1  - Tombor, Lukas
A1  - John, David
A1  - Warwick, Timothy
A1  - Rezende Felipe, Flávia Figueiredo de
A1  - Weigert, Andreas
A1  - Shah, Ajay M.
A1  - Hansmann, Martin-Leo
A1  - Weißmann, Norbert
A1  - Dimmeler, Stefanie
A1  - Schröder, Katrin
A1  - Brandes, Ralf
T1  - The hydrogen-peroxide producing NADPH oxidase 4 does not limit neointima development after vascular injury in mice
T2  - Redox Biology
N2  - Objective: The NADPH oxidase Nox4 is an important source of H2O2. Nox4-derived H2O2 limits vascular inflammation and promotes smooth muscle differentiation. On this basis, the role of Nox4 for restenosis development was determined in the mouse carotid artery injury model. Methods and results: Genetic deletion of Nox4 by a tamoxifen-activated Cre-Lox-system did not impact on neointima formation in the carotid artery wire injury model. To understand this unexpected finding, time-resolved single-cell RNA-sequencing (scRNAseq) from injured carotid arteries of control mice and massive-analysis-of-cDNA-ends (MACE)-RNAseq from the neointima harvested by laser capture microdissection of control and Nox4 knockout mice was performed. This revealed that resting smooth muscle cells (SMCs) and fibroblasts exhibit high Nox4 expression, but that the proliferating de-differentiated SMCs, which give rise to the neointima, have low Nox4 expression. In line with this, the first weeks after injury, gene expression was unchanged between the carotid artery neointimas of control and Nox4 knockout mice. Conclusion: Upon vascular injury, Nox4 expression is transiently lost in the cells which comprise the neointima. NADPH oxidase 4 therefore does not interfere with restenosis development after wire-induced vascular injury.
KW  - NADPH oxidase
KW  - Nox4
KW  - Restenosis
KW  - Reactive oxygen species
KW  - Carotid injury
KW  - Single-cell RNA sequencing
KW  - Inflammation
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63064
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-630644
SN  - 2213-2317
N1  - This work was supported by grants from the Deutsche Forschungsgemeinschaft (GRK 2336, SFB815 (TPA01) and SFB834 (TPA02), Excellence Cluster EXS2026 CPI - Cardiopulmonary Institute). AMS is supported by the British Heart Foundation (CH/1999001/11735).
VL  - 45
IS  - art. 102050
SP  - 1
EP  - 11
PB  - Elsevier
CY  - Amsterdam [u.a.]
ER  -