The hydrogen-peroxide producing NADPH oxidase 4 does not limit neointima development after vascular injury in mice

  • 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.
Author:Giulia Karolin Buchmann, Christoph Schürmann, Manuela Spaeth, Wesley Abplanalp, Lukas Tombor, David JohnORCiDGND, Timothy WarwickORCiD, Flávia Figueiredo de Rezende FelipeORCiDGND, Andreas WeigertORCiDGND, Ajay M. ShahORCiD, Martin-Leo Hansmann, Norbert WeißmannGND, Stefanie DimmelerORCiDGND, Katrin SchröderORCiDGND, Ralf BrandesORCiDGND
Parent Title (English):Redox Biology
Place of publication:Amsterdam [u.a.]
Document Type:Article
Date of Publication (online):2021/06/18
Date of first Publication:2021/06/18
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/03/02
Tag:Carotid injury; Inflammation; NADPH oxidase; Nox4; Reactive oxygen species; Restenosis; Single-cell RNA sequencing
Issue:art. 102050
Page Number:11
First Page:1
Last Page:11
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).
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0