Disruption of USP9X in macrophages promotes foam cell formation and atherosclerosis.

ABSTRACT: Subendothelial macrophage internalization of modified lipids and foam cell formation are hallmarks of atherosclerosis. Deubiquitinating enzymes (DUBs) are involved in various cellular activities; however, their role in foam cell formation is not fully understood. Here, using a loss-of-function lipid accumulation screening, we identified ubiquitin-specific peptidase 9 X-linked (USP9X) as a factor that suppressed lipid uptake in macrophages. We found that USP9X expression in lesional macrophages was reduced during atherosclerosis development in both humans and rodents. Atherosclerotic lesions from macrophage USP9X-deficient mice showed increased macrophage infiltration, lipid deposition, and necrotic core content than control apolipoprotein E-KO (Apoe-/-) mice. Additionally, loss-of-function

SUBMITTER: Wang B 

PROVIDER: S-EPMC9106359 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature