In mice genetically predisposed to atherosclerosis and fed a high-fat diet, a specific peptide called mPN12 that blocks Ninjurin-1 reduces the size of fatty plaques in arteries by about 42.5% and...
Mechanism
Synthesis from 1 study
When fat builds up in arteries, a protein called Ninjurin-1 turns on a chain reaction that makes the artery lining inflamed and sticky, trapping more fat. Blocking Ninjurin-1 stops this chain reaction, so less fat gets trapped and plaques don’t grow — but the artery’s structural strength stays the...
Most probable mechanism
When a protein called Ninjurin-1 builds up in the lining of blood vessels due to high fat levels, it turns on a signaling system that makes the vessel wall inflamed and sticky. This inflammation causes more fat to get trapped inside the vessel wall, forming fatty plaques. Blocking Ninjurin-1 stops this signaling, which calms down the inflammation, reduces the stickiness of the vessel lining, and prevents fat from building up — without weakening the plaque's structural support.
Ninjurin-1 protein expression increases in endothelial cells under conditions of elevated lipid exposure, such as a high-fat diet.
Ninjurin-1 activates the NF-κB signaling pathway by promoting phosphorylation of its p65 subunit, leading to nuclear translocation and transcriptional activation of inflammatory genes.
Activated NF-κB upregulates production of the chemokine CXCL-8 in endothelial cells.
CXCL-8 binds to its receptors on endothelial cells, creating a positive feedback loop that sustains NF-κB activation and amplifies inflammatory signaling.
Sustained NF-κB/CXCL-8 signaling impairs endothelial cell function by reducing proliferation and migration while increasing apoptosis, disrupting vascular homeostasis.
Endothelial dysfunction increases permeability and adhesiveness of the vessel wall, promoting retention and accumulation of lipids within the arterial intima.
Inhibition of Ninjurin-1 interrupts this cascade, reducing lipid deposition and plaque size without altering collagen content in the plaque matrix.
Evidence from Studies
Supporting (1)
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Ninjurin-1 drives atherosclerosis progression via NF-κB/CXCL-8 activation in endothelial cells
Contradicting (0)
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