Antagonism of let-7c reduces atherosclerosis and macrophage lipid accumulation by promoting PGC-1 α/LXRα/ABCA1/G1 pathway

Gene. 2024 Feb 22:148302. doi: 10.1016/j.gene.2024.148302. Online ahead of print.ABSTRACTChanges in circulating let-7c were significantly associated with the alter in lipid profile, but its role in intracellular lipid metabolism remains unknown. This work was conducted to explore the effects of let-7c on the lipid accumulation in macrophages and uncover the underlying mechanism. Our results showed that let-7c inhibition relieved atherosclerosis progression in apoE-/- mice. In ox-LDL-treatment macrophages, let-7c knockdown suppressed lipid accumulation but does no affect cholesterol intake. Consistent with this, overexpression of let-7c promoted lipid accumulation by reducing the expression of LXRα and ABCA1/G1. Mechanistically, let-7c targeted PGC-1α to repress the expression of LXRα and ABCA1/G1, thereby regulating cholesterol homeostasis in macrophages. Taken together, these findings suggest that antagonism of let-7c reduces atherosclerosis and macrophage lipid accumulation through the PGC-1α/LXRα/ABCA1/G1 axis.PMID:38401833 | DOI:10.1016/j.gene.2024.148302

Source: Gene - February 24, 2024 Category: Genetics & Stem Cells Authors: Shuyun Lin Lianjie Hou Yu Wang Huiling Lin Jiefeng Deng Shuang Li Haijiao Long Guojun Zhao Source Type: research