OAS1 induces endothelial dysfunction and promotes monocyte adhesion through the NFκB pathway in atherosclerosis

Area of Science:

• Cardiovascular Biology
• Immunology
• Molecular Medicine

Background:

• Atherosclerosis (AS) pathogenesis involves chronic inflammation and endothelial dysfunction.
• 2'-5'-oligoadenylate synthetase 1 (OAS1) is an inflammation-related protein with an unclear role in AS.
• Mitigating endothelial dysfunction and monocyte adhesion is key to impeding AS progression.

Purpose of the Study:

• To investigate the role of OAS1 in endothelial dysfunction and monocyte adhesion in atherosclerosis.
• To explore the relationship between OAS1, NFκBp65, and AS development.
• To assess OAS1 as a potential therapeutic target for AS.

Main Methods:

• Bioinformatic analysis of human aortic sections for OAS1 enrichment.
• In vitro studies involving lipopolysaccharide (LPS) stimulation and OAS1 deficiency/knockdown.
• Assessment of reactive oxygen species (ROS), nitric oxide (NO), monocyte adhesion, and NFκBp65 expression.

Main Results:

• OAS1 is enriched in human atherosclerotic plaques, with higher levels in advanced stages.
• OAS1 expression is upregulated by LPS in a time- and concentration-dependent manner.
• OAS1 deficiency attenuated LPS-induced ROS, NO changes, and monocyte adhesion.
• OAS1 positively correlates with NFκBp65 in plaques; OAS1 deletion downregulates P65.
• Combined OAS1 and NFκBp65 knockdown significantly ameliorated endothelial dysfunction and monocyte adhesion.

Conclusions:

• OAS1 plays a significant role in promoting endothelial dysfunction and monocyte adhesion in AS.
• OAS1 modulates these processes partly through the regulation of NFκBp65.
• OAS1 represents a potential therapeutic target for managing atherosclerosis.