Publication Date:
2019
Description:
〈p〉Macrophages drive atherosclerotic plaque progression and rupture; hence, attenuating their atherosclerosis-inducing properties holds promise for reducing coronary heart disease (CHD). Recent studies in mouse models have demonstrated that Tribbles 1 (Trib1) regulates macrophage phenotype and shows that 〈i〉Trib1〈/i〉 deficiency increases plasma cholesterol and triglyceride levels, suggesting that reduced 〈i〉TRIB1〈/i〉 expression mediates the strong genetic association between the 〈i〉TRIB1〈/i〉 locus and increased CHD risk in man. However, we report here that myeloid-specific 〈i〉Trib1〈/i〉 (m〈i〉Trib1〈/i〉) deficiency reduces early atheroma formation and that m〈i〉Trib1〈/i〉 transgene expression increases atherogenesis. Mechanistically, m〈i〉Trib1〈/i〉 increased macrophage lipid accumulation and the expression of a critical receptor (OLR1), promoting oxidized low-density lipoprotein uptake and the formation of lipid-laden foam cells. As 〈i〉TRIB1〈/i〉 and 〈i〉OLR1〈/i〉 RNA levels were also strongly correlated in human macrophages, we suggest that a conserved, TRIB1-mediated mechanism drives foam cell formation in atherosclerotic plaque and that inhibiting mTRIB1 could be used therapeutically to reduce CHD.〈/p〉
Electronic ISSN:
2375-2548
Topics:
Natural Sciences in General
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