In zebrafish with high cholesterol, changes in specific inflammatory molecules in blood vessel lining occur before immune cells and fat build up in the vessels, suggesting a sequence of early events...
Mechanism
Synthesis from 1 study
Too much cholesterol turns off a protective signal in blood vessel walls, which lets inflammation start. That inflammation pulls in immune cells that trap cholesterol, causing fatty buildup. This sequence happens in a fixed order, and turning the protective signal back on stops the whole process.
Most probable mechanism
When too much cholesterol builds up in the blood, it causes the inner lining of blood vessels to turn off a protective switch called PPARγ. Without this switch, inflammatory signals like TNF-α and IL-1β turn on, making the vessel wall sticky and attracting immune cells. These immune cells then trap cholesterol in the vessel wall, leading to fatty buildup.
Systemic hyperlipidemia from dietary cholesterol overload reduces PPARγ expression in vascular endothelial cells
Reduced PPARγ activity removes transcriptional repression of pro-inflammatory genes, leading to increased expression of TNF-α and IL-1β in endothelial cells
Elevated TNF-α and IL-1β promote endothelial activation, increasing expression of adhesion molecules and chemokines that recruit neutrophils
Neutrophil accumulation in the vessel wall enhances lipid retention through enzymatic and physical disruption of endothelial integrity
Trapped lipids accumulate and form deposits within the vessel wall, initiating early atherogenic lesions
Evidence from Studies
Supporting (1)
Community contributions welcome
Chronological in vivo imaging reveals endothelial inflammation prior to neutrophils accumulation and lipid deposition in HCD-fed zebrafish.
Contradicting (0)
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