γ-Glutamylcysteine Inhibits VSMC-Derived Foam Cell Formation via Upregulating Thioredoxin-1 Expression

Abstract

The formation and accumulation of foam cells within the arterial wall is the main early event of atherosclerosis. Vascular smooth muscle cells (VSMCs) are the most abundant cells in human atherosclerotic lesions and are suggested to contribute to atheroma foam cells. γ-glutamylcysteine (γ-GC), as an immediate precursor of glutathione, exhibits anti-inflammatory and antioxidant effects. However, the effects of γ-GC on the formation of atherosclerotic plaques are not yet clarified. Here, we display the effects of γ-GC against ox-LDL-induced formation of foamy VSMCs. Our results showed that γ-GC apparently reduced the total intracellular cholesterol content in mouse and rat VSMCs. The oil red O and fluorescent BODIPY staining indicated that γ-GC inhibited the formation of foam cell. Mechanistically, γ-GC reduced the expression of macrophage scavenger receptor 1 (Msr1) in VSMCs to attenuate cholesterol uptake by the cells. Further RNA-seq analysis, and immunofluorescence as well as immunoblotting measurements showed that thioredoxin-1 (Txn1) was important for γ-GC to reduce Msr1 expression in VSMCs and lipid uptake by the cells. Overall, our research indicated that γ-GC increases Txn1 expression, which causes scavenger receptor A reduction and lipid uptake inhibition in ox-LDL-stimulated VSMCs. Our study revealed that γ-GC has potential for the prevention of atherosclerosis.