Atherosclerosis (AS), a common arterial disease, is one of the main pathological roots of cardiovascular disease. The formation and accumulation of foam cells is an important event in early AS. An imbalance between cholesterol uptake and efflux is the primary cause of foam cell formation. Although research has focused on preventing the formation of foam cells, a safe and effective therapy has to be found. Zafirlukast is a widely useful type 1 cysteinyl leukotriene receptor (CysLT1R) antagonist with a good safety profile. Zafirlukast is the most used for the treatment of asthma and allergic rhinitis. However, the effect of zafirlukast on preventing the formation of foam cells has not been determined. The aim of this study was to investigate whether zafirlukast prevented macrophages from transforming into foam cells. Our data show that zafirlukast reduced the expression of CD36 and lipoprotein receptor-1 (LOX-1), which are responsible for lipid uptake. In addition, zafirlukast enhanced the activity of ATP-Binding Cassette A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1), leading to the acceleration of cholesterol efflux. Furthermore, zafirlukast influenced the activity of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway, which mediates the expression of ABCA1 and ABCG1. In summary, our data indicate that zafirlukast might be a potential treatment strategy for AS by mediating lipid metabolism and preventing the formation of foam cells.
Keywords: ABCA1; ABCG1; Atherosclerosis; CD36; LOX-1; PI3K/AKT; Scavenger receptor.
Copyright © 2020. Published by Elsevier Inc.