Protective effects of phenethyl isothiocyanate on foam cell formation by combined treatment of oxidized low-density lipoprotein and lipopolysaccharide in THP-1 macrophage

Food Sci Nutr. 2021 May 4;9(6):3269-3279. doi: 10.1002/fsn3.2293. eCollection 2021 Jun.

Abstract

Accumulation of cholesterol-laden macrophage foam cells characteristic of early stage atherosclerotic lesions. Phenethyl isothiocyanate (PEITC) is a naturally occurring isothiocyanate found in cruciferous vegetables that has reported a variety of activities including antioxidant and anti-inflammatory properties. However, the protective effect of PEITC on foam cell formation and its precise mechanism is not yet clear. Therefore, we investigated whether PEITC suppresses foam cell formation and regulates the expression of genes related to lipid accumulation, cholesterol efflux, and inflammation in THP-1 derived-macrophages. We exposed THP-1 derived-macrophages to oxidized low-density lipoprotein (ox-LDL) (20 μg/mL) and lipopolysaccharide (LPS) (500 ng/ml) to mimic foam cell formation. Here, PEITC downregulated the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), cluster of differentiation 36 (CD36), scavenger receptor A1 (SR-A1), and nuclear factor-κB (NF-κB), while upregulated ATP binding cassette subfamily A member 1 (ABCA1)/liver-X-receptor α (LXR-α)/peroxisome proliferator-activated receptor gamma (PPARγ) and sirtuin 1 (SIRT1) expression compared to co-treated with ox-LDL and LPS. Taken together, PEITC, at least in part, inhibits foam cell formation and reduces lipid accumulation in foam cells. Therefore, we suggest that PEITC may be a potential candidate for the treatment and prevention of vascular inflammation and atherosclerosis.

Keywords: atherosclerosis; foam cells; lipopolysaccharides; oxidized low density lipoprotein; phenethyl isothiocyanate; scavenger receptor.