Deletion of NoxO1 limits atherosclerosis development in female mice

Area of Science:

• Cardiovascular Research
• Oxidative Stress Biology
• Molecular Medicine

Background:

• Oxidative stress is a known risk factor for atherosclerosis.
• NADPH oxidases (Nox) produce reactive oxygen species (ROS), but their specific roles in atherosclerosis are not fully understood.
• While Nox2 promotes and Nox4 limits atherosclerosis, the contribution of Nox1 and its cofactors, like NoxO1, remains less clear.

Purpose of the Study:

• To investigate the role of the essential cytosolic cofactor NoxO1 in the development of atherosclerosis.
• To define the function of the Nox1/NoxO1 system in cardiovascular disease progression.

Main Methods:

• Utilized wildtype (WT) and NoxO1 knockout mice.
• Induced hypercholesterolemia and atherosclerosis using a high-fat diet and adeno-associated virus (AAV)-mediated PCSK9 overexpression.
• Analyzed atherosclerosis formation in the brachiocephalic artery and aortic arch, and assessed plasma cytokine profiles.

Main Results:

• Deletion of NoxO1 reduced atherosclerosis in female, but not male, mice compared to WT littermates.
• A reduced pro-inflammatory cytokine signature was observed in the plasma of female NoxO1 knockout mice.
• Vessel-based MACE-RNAseq did not confirm this inflammatory signature, and Nox1/NoxO1 system expression was low.

Conclusions:

• The scaffolding protein NoxO1 plays a role in atherosclerosis development, particularly in female mice.
• NoxO1 may attenuate the global inflammatory burden, thereby influencing atherosclerosis progression.
• Further research is needed to fully elucidate the mechanisms by which NoxO1 impacts cardiovascular disease.