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

Autor: Norbert Weissmann, Andreas Weigert, Ralf P. Brandes, David John, Flávia Rezende, Timothy Warwick, Wesley Abplanalp, Ajay M. Shah, Stefanie Dimmeler, Martin-Leo Hansmann, Manuela Spaeth, Katrin Schröder, Giulia K. Buchmann, Christoph Schürmann, Lukas Tombor
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Pathology
Medicine (General)
Clinical Biochemistry
Biochemistry
Single-cell RNA sequencing
Mice
0302 clinical medicine
Restenosis
Biology (General)
Cells
Cultured
Laser capture microdissection
Mice
Knockout
chemistry.chemical_classification
NADPH oxidase
biology
Carotid injury
NOX4
NADPH Oxidase 4
CTL
Control
Knockout mouse
cardiovascular system
scRNAseq
Single cell RNA sequencing
SMC
smooth muscle cells
medicine.symptom
Research Paper
Neointima
medicine.medical_specialty
QH301-705.5
Myocytes
Smooth Muscle
Inflammation
03 medical and health sciences
Nox4
R5-920
ddc:570
medicine
Animals
MACE
massive-analysis-of-cDNA-ends
ddc:610
cardiovascular diseases
Reactive oxygen species
urogenital system
Organic Chemistry
Hydrogen Peroxide
Vascular System Injuries
medicine.disease
030104 developmental biology
chemistry
biology.protein
030217 neurology & neurosurgery
ROS
Reactive oxygen species
Zdroj: Redox Biology, Vol 45, Iss, Pp 102050-(2021)
Redox Biology
ISSN: 2213-2317
Popis: 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.
Graphical abstract Image 1
Databáze: OpenAIRE
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