Atheroprotective Effect of Fucoidan in THP-1 Macrophages by Potential Upregulation of ABCA1

Abstract

Targeting foam cells reduces the risk and pathophysiology of atherosclerosis, of which they are one of its early hallmarks. The precise mechanism of action of fucoidan, a potential anti-atherogenic drug, is still unknown. Our objective was to assess the ability of fucoidan to regulate expression of ATP-binding cassette transporter A1 (ABCA1) in ox-LDL-induced THP-1 macrophages. Molecular docking was used to predict how fucoidan interacts with anti-foam cell markers, and further in vitro experiments were performed to evaluate the protective effect of fucoidan on modulating uptake and efflux of lipids. THP-1 macrophages were protected by 50 µg/mL of fucoidan and were then induced to form foam cells with 25 µg/mL of ox-LDL. Expression levels were assessed using RT-qPCR, and an Oil Red O stain was used to observe lipid accumulation in THP-1 macrophages. In addition, ABCA1 protein was examined by Western blot, and cellular cholesterol efflux was determined using fluorescently labeled cholesterol. Under a light microscope, decreased lipid accumulation in ox-LDL-induced-THP-1 macrophages pre-treated with fucoidan showed a significant effect, although it did not affect the expression of scavenger receptors (SR-AI and CD36). It is interesting to note that fucoidan dramatically increased the gene and protein expression of ABCA1, perhaps via the liver X receptor-α (LXR-α). Moreover, fucoidan’s ability to increase and control the efflux of cholesterol from ox-LDL-induced THP-1 macrophages revealed how it may alter ABCA1’s conformation and have a major effect on how it interacts with apolipoprotein A (ApoA1). In vitro results support a rationale for predicting fucoidan and its interaction with its receptor targets’ predicted data, hence validating its anti-atherogenic properties and suggesting that fucoidan could be promising as an atheroprotective.