The buildup of fats and plaques in artery walls requires prior inflammation of the inner lining of blood vessels.
Mechanism
Synthesis from 3 studies
When too much fat builds up in the blood, it damages the inner lining of arteries, causing the cells to change shape and start making inflammatory signals. These signals trap more fat and attract immune cells, while the damaged cells themselves begin storing fat inside, forming the earliest...
Most probable mechanism
When the inner lining of arteries is stressed by excess fat in the blood, it becomes inflamed and starts behaving abnormally. This causes the cells to change shape, move key parts of their internal machinery into the nucleus, and start making more inflammatory signals and fat droplets inside themselves. These signals attract immune cells and make the artery wall sticky, so more fat gets trapped. The inflamed cells also lose their normal function and turn into fat-filled cells that form the earliest signs of plaque.
Metabolic stress from elevated lipids disrupts endothelial cell structure and cytoskeletal organization, leading to abnormal cell morphology and spatial confinement.
Disrupted cytoskeletal integrity triggers relocalization of Golgi components and COPII vesicles from the cytoplasm into the nucleus.
Nuclear translocation of Golgi and COPII components facilitates the accumulation of ribosomal protein RPL23 in the nucleolus, enhancing ribosomal biogenesis and translational capacity.
Increased translational activity in the nucleolus drives elevated synthesis and secretion of proinflammatory cytokines including IL-6, MCP-1, and CXCL-8.
Inflammatory cytokines activate NF-κB signaling in endothelial cells, creating a self-reinforcing loop that sustains inflammation and suppresses endothelial repair functions.
Downregulation of PPARγ removes anti-inflammatory repression, further amplifying expression of TNF-α and IL-1β and promoting a chronic proinflammatory state.
Sustained inflammation impairs endothelial barrier integrity, reduces cell proliferation and migration, and increases apoptosis, leading to endothelial dysfunction.
Aberrant intracellular lipid synthesis occurs due to nuclear-localized Golgi and COPII machinery, resulting in accumulation of large lipid droplets within endothelial cells.
Lipid-laden endothelial cells lose endothelial markers and adopt a foam cell-like phenotype, while secreted chemokines recruit neutrophils that further promote lipid retention in the vessel wall.
Evidence from Studies
Supporting (3)
Community contributions welcome
Stacked human aortic endothelial cells induce atherosclerotic fatty streaks and release proinflammatory cytokines and chemokines
Ninjurin-1 drives atherosclerosis progression via NF-κB/CXCL-8 activation in endothelial cells
Chronological in vivo imaging reveals endothelial inflammation prior to neutrophils accumulation and lipid deposition in HCD-fed zebrafish.
Contradicting (0)
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