When human aortic endothelial cells are grown in stacked layers in a lab, they change shape and accumulate lipid droplets at about ten times the level of cells grown in single layers, while also...
Mechanism
Synthesis from 1 study
When endothelial cells are stacked on top of each other, their internal machinery gets scrambled, forcing parts of their fat-making equipment into the nucleus. This causes them to overproduce fat and inflammatory signals while losing their normal identity, turning them into fat-storing cells that...
Most probable mechanism
When endothelial cells are piled up in three dimensions, their internal structure gets disrupted, causing parts of their lipid-making machinery to move into the nucleus. This triggers the nucleus to produce more lipids and inflammatory signals, while the cells lose their normal identity markers and start storing fat like foam cells, even without any external cholesterol.
Spatial confinement from 3D stacking disrupts cytoskeletal organization, leading to loss of normal cell shape and polarity
Cytoskeletal disruption causes Golgi apparatus components and COPII vesicles to translocate from the cytoplasm into the nucleus
Nuclear translocation of Golgi components facilitates the entry of ribosomal protein RPL23 into the nucleolus, enhancing ribosomal biogenesis and translational capacity
Increased translational activity in the nucleolus drives overproduction of proinflammatory cytokines and enzymes involved in lipid synthesis
Aberrant lipid synthesis occurs within autophagic vacuoles and leads to massive accumulation of lipid droplets, tenfold higher than in normal cells
Lipid overload and organelle mislocalization suppress expression of endothelial identity markers CD31 and FVIII, resulting in phenotypic de-differentiation toward a foam cell-like state
Evidence from Studies
Supporting (1)
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Stacked human aortic endothelial cells induce atherosclerotic fatty streaks and release proinflammatory cytokines and chemokines
Contradicting (0)
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