Endothelial NADPH oxidase 5 overexpression promotes thrombosis and alters thrombus composition by sex-dependent mechanisms in mice.

Background: Different members of the NADPH oxidases family (NOXs) participate in thrombosis. Nevertheless, the information about NOX5 in this process is scarce. The aim of this study was to test whether chronic expression of NOX5 may modulate thrombosis.

Methods: To test this hypothesis, mice expressing human NOX5 at the endothelium and their control littermates underwent a FeCl₃-induced thrombosis model in the carotid artery. The composition of the thrombi obtained from these mice was analysed by proteomics. The derived findings were corroborated by molecular analysis in vivo, in vitro and ex vivo. Finally, the antithrombic effects of N-acetylcysteine (NAC) and the pan-NOX inhibitor ML090 were tested.

Results: The results from the present assay indicate that endothelial NOX5 expression promotes thrombosis in vivo in a sex-dependent manner. In female mice, NOX5 enhances prostaglandin E₂ (PGE₂) secretion and alters the expression of endothelial adhesion molecules. In male mice, NOX5 partially promotes the activation of circulating neutrophils. Both, NAC and ML090 protect against thrombosis in vivo.

Conclusions: In conclusion, our findings demonstrate that endothelial NOX5 plays a role in thrombosis, indicating that this oxidase should be considered as a therapeutic target to prevent thrombosis.