Tribbles homolog 1 enhances cholesterol efflux from oxidized low-density lipoprotein-loaded THP-1 macrophages

Abstract

Macrophage foam cell formation plays a pivotal role in the pathogenesis of atherosclerosis. The protein Tribbles homolog 1 (Trib1), a member of the Tribbles protein family, functions as an adaptor or scaffold protein. Recent studies have indicated its implication in lipoprotein metabolism. In the present study, the role of Trib1 in macrophage foam cell formation was investigated. Oil red O staining was used to analyze intracellular lipid deposition, while the effects of Trib1 overexpression on cholesterol efflux were also examined. Furthermore, quantitative polymerase chain reaction and western blot analysis were performed to measure the expression levels of genes involved in cholesterol efflux. The results revealed that overexpression of Trib1 inhibited lipid accumulation in oxidized low density lipoprotein-treated THP-1 macrophages and facilitated macrophage cholesterol efflux to apolipoprotein A-I. Overexpression of Trib1 also upregulated the expression levels of ATP-binding cassette A1 (ABCA1), ABCG1, liver X receptor α (LXRα) and peroxisome proliferator-activated receptor γ (PPARγ). In addition, silencing of LXRα or PPARγ via small interfering RNA transfection significantly reversed the Trib1-induced cholesterol efflux. In conclusion, Trib1 inhibits macrophage foam cell formation and enhances cholesterol efflux, which is associated with regulation of the PPARγ, LXRα, ABCA1 and ABCG1 expression levels.