Effect Of Atorvastation On THP-1 Macrophage Lipid Accumulation And The Possible Mechanism

BACGROUND Scavenger receptor-mediated accumulation of oxLDL-C is considered to be a critical step in the development of atherosclerotic foam cell formation. The class B scavenger receptor, CD36, is identified as the major receptor for oxidized low density lipoprotein(oxLDL). Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of nuclear hormone receptor superfamily. PPARγ has been implicated in such diverse pathways as lipid metabolism and glucose homeostasis, promoting adipocyte, monocyte/macrophage differentiation, inhibiting inflammation. PPARy heterodimerizes with the retinoid X receptor (RXR) and functions as a transcriptional regulator of genes that modulate lipid metabolism and adipocyte gene expression. OxLDL could upregulate CD36 expression by activating PPARγ in THP-1 macrophage. PPARγ -CD36 pathway plays an important effect in oxLDL-uptake of THP-1 macrophage and atherosclerotic foam cell formation. Atorvastatin has various effects in preventing and treating cardiovascular diseases, such as endothelial normalization, anti-inflammatory effects, inhibition of LDL oxidation, stabilization of atherosclerotic plaque, inhibition of platelet thrombus formation and the scavenger receptor expression. The study is aimed to investigate the effect of atorvastatin on THP-1 macrophage lipid accumulation and the possible mechanism.OBJECTIVE To investigate the effects of atorvastatin on cholesterol influx and CD36 expression in THP-1 macrophages, the effects of atorvastatin on oxLDL-induced lipid accumulation and CD36, PPARγ expression in THP-1 macrophages, the effects atorvastatin , PPARγ agonist and antagonist on cholesterol accumulation and the expression of CD36, PPAR γ and PPARγ -Pi in THP-1 macrophages.METHODS THP-1 macrophages were induced to differentiation into macrophages by...