Tribbles 3 deficiency promotes atherosclerotic fibrous cap thickening and macrophage-mediated extracellular matrix remodelling.

ABSTRACT: Tribbles 3 (TRIB3) modulates lipid and glucose metabolism, macrophage lipid uptake, with a gain-of-function variant associated with increased cardiovascular risk. Here we set out to examine the role of this pseudokinase in atherosclerotic plaque development. Human endarterectomy atherosclerotic tissue specimens analysed by immunofluorescence showed upregulated TRIB3 in unstable plaques and an enrichment in unstable regions of stable plaques. Atherosclerosis was induced in full body Trib3^KO and Trib3^WT littermate mice by injecting mPCSK9 expressing adeno-associated virus and western diet feeding for 12 weeks. Trib3^KO mice showed expanded visceral adipose depot while circulatory lipid levels remained unaltered compared to wildtype mice. <

SUBMITTER: Martinez-Campesino L 

PROVIDER: S-EPMC9505024 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature