APOC3 promotes TNF-α-induced expression of JAM-1 in endothelial cell via PI3K-IKK2-p65 pathway

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Inflammation Research

Background:

• Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation.
• Apolipoprotein C3 (APOC3) regulates lipid metabolism and is linked to vascular inflammation in atherosclerosis.
• Previous work showed APOC3 elevates tumor necrosis factor-alpha (TNF-α) in endothelial cells.

Purpose of the Study:

• To investigate the APOC3 signaling pathway mediating TNF-α-induced expression of JAM-1 in human umbilical vein endothelial cells (HUVECs).

Main Methods:

• HUVECs were treated with APOC3 (50 μg/ml) for 16 hours.
• TNF-α gene was silenced using lentiviral TNF-α-shRNA.
• Eight signaling pathway inhibitors were used to block APOC3 effects.
• JAM-1 expression was assessed via qRT-PCR, Western blotting, and flow cytometry.
• IKK2 degradation and NF-κB p65 phosphorylation were analyzed by Western blotting.

Main Results:

• APOC3 significantly enhanced TNF-α-induced JAM-1 expression in HUVECs.
• APOC3 treatment led to NF-κB p65 upregulation and IκB degradation.
• Inhibiting APOC3 reversed the TNF-α-induced overexpression of JAM-1.
• APOC3 induced JAM-1 expression through the NF-κB, IKK2, and PI3K signaling pathways.

Conclusions:

• APOC3 promotes JAM-1 expression in HUVECs.
• The APOC3-mediated pathway involves TNF-α, NF-κB, IKK2, and PI3K signaling.
• These findings elucidate a novel mechanism in APOC3-driven vascular inflammation relevant to atherosclerosis.