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

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Giulia K. Buchmann, Christoph Schürmann, Manuela Spaeth, Wesley Abplanalp, Lukas Tombor, David John, Timothy Warwick, Flávia Rezende, Andreas Weigert, Ajay M. Shah, Martin Leo Hansmann, Norbert Weissmann, Stefanie Dimmeler, Katrin Schröder, Ralf P. Brandes

Original languageEnglish
Pages (from-to)102050
Number of pages1
JournalRedox Biology
Volume45
DOIs
Published1 Sep 2021

Bibliographical note

Publisher Copyright: Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved. Copyright: This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine

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Abstract

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.

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