Triglyceride Down-regulates Expression of MSR-1 in PMA-induced THP-1 Macrophages

Abstract

Atherosclerosis is a cardiovascular disease in which plaque builds up inside of an artery and can lead to various complications such as myocardial infarction, stroke, and thrombosis. Recently, hypertriglyceridemia has attracted significant attention as contributors to development of atherosclerosis. However, molecular mechanism of its contribution to atherosclerosis is poorly understood. Here we proposed a potential link between triglyceride (TG) and atherosclerosis. TG treatment promoted downregulation of certain scavenger receptor, macrophage scavenger receptor-1 (MSR-1) in phorbol myristate acetate (PMA)-derived human macrophages. TG treatment caused reduction of MSR-1 mRNA expression in a time-and dose-dependent manner. Using chemical inhibitors, we found that inhibition of signaling pathways associated with PI3K and PLC enhances TG-induced reduction of MSR-1 expression in THP-1 macrophages implying that PI3K and PLC is implicated in the expression of MSR-1 in macrophages. Since MSR-1 is associated with uptake and clearance of atherogenic lipoprotein, oxidized low density lipoprotein (oxi-LDL), our data suggest that increase of oxi-LDL due to TG-mediated reduction of its receptor MSR-1 can promote atherosclerosis.