Journal
REDOX BIOLOGY
Volume 37, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.redox.2020.101713
Keywords
NADPH oxidase; NoxO1; Atherosclerosis; Gender differences; PCSK9; Reactive oxygen species
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Funding
- Deutsche Forschungsgemeinschaft (Auflosung von Entzundungen)
- German Center for Cardiovascular Research [81X220014, 81X2700221]
- National Institutes of Health [HL119798, HL095070]
- Deutsche Forschungsgemeinschaft (excellence cluster EXS2026 Cardio-Pulmonary Institute)
- Deutsche Forschungsgemeinschaft [GRK 2336, Sonderforschungsbereich 834 -Teilproject A2]
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Objective: Oxidative stress is a risk factor for atherosclerosis. NADPH oxidases of the Nox family produce ROS but their contribution to atherosclerosis development is less clear. Nox2 promotes and Nox4 rather limits atherosclerosis. Although Nox1 with its cytosolic co-factors are largely expressed in epithelial cells, a role for Nox1 for atherosclerosis development was suggested. To further define the role of this homologue, the role of its essential cytosolic cofactor, NoxO1, was determined for atherosclerosis development with the aid of knockout mice. Methods and results: Wildtype (WT) and NoxO1 knockout mice were treated with high fat diet and adeno-associated virus (AAV) overexpressing pro-protein convertase subtilisin/kexin type 9 (PCSK9) to induce hepatic low-density lipoprotein (LDL) receptor loss. As a result, massive hypercholesterolemia was induced and spontaneous atherosclerosis developed within three month. Deletion of NoxO1 reduced atherosclerosis formation in brachiocephalic artery and aortic arch in female but not male NoxO1(-/-) mice as compared to WT littermates. This was associated with a reduced pro-inflammatory cytokine signature in the plasma of female but not male NoxO1(-/-) mice. MACE-RNAseq of the vessel did not reveal this signature and the expression of the Nox1/NoxO1 system was low to not detectable. Conclusions: The scaffolding protein NoxO1 plays some role in atherosclerosis development in female mice probably by attenuating the global inflammatory burden. Conclusions: The scaffolding protein NoxO1 plays some role in atherosclerosis development in female mice probably by attenuating the global inflammatory burden.
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