Maslinic acid suppresses macrophage foam cells formation: Regulation of monocyte recruitment and macrophage lipids homeostasis

The transformation of macrophages to foam cells is a critical component in atherosclerotic lesion formation. Maslinic acid (MA), a novel natural pentacyclic triterpene, has cardioprotective and anti-inflammatory properties. It is hypothesized that MA can suppress monocyte recruitment to endothelial cells and inhibit macrophage foam cells formation. Previous study shows that MA inhibits inflammatory effects induced by sPLA2-IIA, including foam cells formation. This study elucidates the regulatory effect of MA in monocyte recruitment, macrophage lipid accumulation and cholesterol efflux. Our findings demonstrate that MA inhibits THP-1 monocyte adhesion to HUVEC cells in a TNFα-dependent and independent manner, but it induces trans-endothelial migration marginally at low concentration. MA down-regulates both gene and protein expression on VCAM-1 and MCP-1 in HUVECs. We further showed that MA suppresses macrophage foam cells formation, as indicated from the Oil-Red-O staining and flow cytometric analysis of intracellular lipids accumulation. The effects observed may be attributed to the antioxidant properties of MA where it was shown to suppress CuSO₄-induced lipid peroxidation. MA inhibits scavenger receptors SR-A and CD36 expression while enhancing cholesterol efflux. MA enhances cholesterol efflux transporters ABCA1 and ABCG1 genes expression marginally without inducing its protein expression. In this study, MA was shown to target important steps that contribute to foam cell formation, including its ability in reducing monocytes adhesion to endothelial cells and LDL peroxidation, down-regulating scavenger receptors expression as well as enhancing cholesterol efflux, which might be of great importance in the context of atherosclerosis prevention and treatment.