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.

OBJECTIVES

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 analyzed by proteomics. The derived findings were corroborated by molecular analysis in vivo, in vitro, and ex vivo. Finally, the antithrombic effects of N-acetylcysteine and the pan-NOX inhibitor ML090 were tested.

RESULTS

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

CONCLUSION

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.