In zebrafish with high cholesterol, inflammation in blood vessel lining involves reduced levels of PPARγ and elevated levels of TNF-α and IL-1β, which together form a detectable molecular pattern of...
Mechanism
Synthesis from 1 study
Too much cholesterol in the blood turns off a natural brake on inflammation inside blood vessel walls. Once that brake is off, inflammatory signals surge, turning the vessel lining inflamed even before immune cells show up or fat starts to stick. This is the earliest sign of blood vessel damage.
Most probable mechanism
When there is too much cholesterol in the blood, it causes a protective molecule in blood vessel lining cells to decrease. This loss lets inflammatory signals rise, which turns the vessel lining into a state of inflammation before any immune cells arrive or fat builds up.
Excess cholesterol in the bloodstream enters vascular endothelial cells and disrupts normal regulatory signaling.
This disruption leads to reduced expression of PPARγ, a transcription factor that normally suppresses inflammatory gene activity.
Loss of PPARγ removes transcriptional repression of pro-inflammatory genes, allowing increased production of TNF-α and IL-1β within endothelial cells.
Elevated TNF-α and IL-1β activate endothelial inflammatory pathways, including adhesion molecule expression and chemokine release.
The inflamed endothelium generates signals that recruit immune cells and promote lipid retention in the vessel wall.
Evidence from Studies
Supporting (1)
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Chronological in vivo imaging reveals endothelial inflammation prior to neutrophils accumulation and lipid deposition in HCD-fed zebrafish.
Contradicting (0)
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