Nucleophosmin contributes to vascular inflammation and endothelial dysfunction in atherosclerosis progression

Area of Science:

• Cardiovascular Biology
• Molecular Medicine

Background:

• The role of nucleophosmin (NPM) in cardiovascular disease, specifically atherosclerosis, remains largely undefined.
• Understanding NPM's mechanisms in atherosclerosis is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the role and underlying mechanisms of NPM in the development of atherosclerosis.

Main Methods:

• NPM levels and localization were assessed in human carotid plaques and controls using molecular biology techniques.
• Atherosclerosis was modeled in ApoE knockout mice fed a Western diet, with NPM knockdown via small hairpin RNA.
• Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies involving palmitic acid stimulation.

Main Results:

• NPM levels were significantly higher in human atherosclerotic plaques, primarily in endothelial cells.
• NPM knockdown in vivo reduced atherosclerotic lesions, stabilized plaques, decreased vascular inflammation, and improved endothelial function.
• NPM knockdown attenuated palmitic acid-induced inflammation and monocyte adhesion in HUVECs by inhibiting NF-κB signaling.

Conclusions:

• NPM promotes atherosclerosis by inducing vascular inflammation and endothelial dysfunction through the NF-κB signaling pathway.
• NPM represents a potential therapeutic target for the prevention and treatment of atherosclerosis.