Journal article
Authors list: Buchmann, Giulia K.; Schuermann, Christoph; Spaeth, Manuela; Abplanalp, Wesley; Tombor, Lukas; John, David; Warwick, Timothy; Rezende, Flavia; Weigert, Andreas; Shah, Ajay M.; Hansmann, Martin-Leo; Weissmann, Norbert; Dimmeler, Stefanie; Schroeder, Katrin; Brandes, Ralf P.
Publication year: 2021
Journal: Redox Biology
Volume number: 45
ISSN: 2213-2317
Open access status: Gold
DOI Link: https://doi.org/10.1016/j.redox.2021.102050
Publisher: Elsevier
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.
Abstract:
Citation Styles
Harvard Citation style: Buchmann, G., Schuermann, C., Spaeth, M., Abplanalp, W., Tombor, L., John, D., et al. (2021) The hydrogen-peroxide producing NADPH oxidase 4 does not limit neointima development after vascular injury in mice, Redox Biology, 45, Article 102050. https://doi.org/10.1016/j.redox.2021.102050
APA Citation style: Buchmann, G., Schuermann, C., Spaeth, M., Abplanalp, W., Tombor, L., John, D., Warwick, T., Rezende, F., Weigert, A., Shah, A., Hansmann, M., Weissmann, N., Dimmeler, S., Schroeder, K., & Brandes, R. (2021). The hydrogen-peroxide producing NADPH oxidase 4 does not limit neointima development after vascular injury in mice. Redox Biology. 45, Article 102050. https://doi.org/10.1016/j.redox.2021.102050
Keywords
Carotid injury; IV; NAD(P)H OXIDASE; NADPH OXIDASE; Nox4; NOX4 PROMOTER; RESTENOSIS; Single-cell RNA sequencing; TRANSFORMING-GROWTH-FACTOR-BETA-1
