Atorvastatin upregulates apolipoprotein M expression via attenuating LXRα expression in hyperlipidemic apoE-deficient mice

摘要

Apolipoprotein M (apoM) is a recently identified human apolipoprotein that is associated with the formation of high-density lipoprotein (HDL). Studies have demonstrated that statins may affect the expression of apoM; however, the regulatory effects of statins on apoM are controversial. Furthermore, the underlying mechanisms by which statins regulate apoM remain unclear. In the present study, in vivo and in vitro models were used to investigate whether the anti-atherosclerotic effects of statins are associated with its apoM-regulating effects and the underlying mechanism. Hyperlipidemia was induced by in apolipoprotein E-deficient mice by providing a high-fat diet. Atorvastatin was administered to hyperlipidemic mice and HepG2 cells to investigate its effect on apoM expression. The liver X receptor α (LXRα) agonist T0901317 was also administered together with atorvastatin to hyperlipidemic mice and HepG2 cells. The results revealed that atorvastatin increased apoM expression, which was accompanied with decreased expression of LXRα in the liver of hyperlipidemic apolipoprotein E-deficient mice and HepG2 cells. Additionally, apoM upregulation was inhibited following treatment with T0901317. In summary, atorvastatin exhibited anti-atherosclerotic effects by upregulating apoM expression in hyperlipidemic mice, which may be mediated by the inhibition of LXRα.