Effect of simvastatin on the expression and regulation mechanism of apolipoprotein M.
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Yang L, Zhao S
Effect of simvastatin on the expression and regulation mechanism of apolipoprotein M.
Int J Mol Med. 2012 Mar;29(3):510-4. doi: 10.3892/ijmm.2011.853. Epub 2011 Dec 5.
- PubMed ID
- 22160096 [ View in PubMed]
- Abstract
Apolipoprotein M (ApoM) is a recently discovered human apolipoprotein predominantly present in high-density lipoprotein (HDL) in the plasma. Statins have effects on many HDL-associated apolipoproteins. However, it is unknown whether statins have effects on ApoM. In the present study, we investigated the effects of simvastatin on ApoM expression and the underlying mechanism(s). Simvastatin up-regulated hepatic ApoM mRNA and protein expression in mice. In HepG2 cells, simvastatin significantly enhanced ApoM mRNA and protein expression in a dose-dependent manner. Simvastatin increased hepatic hepatocyte nuclear factor-1alpha (HNF-1alpha) mRNA and reduced liver X receptor-alpha (LXRalpha) mRNA expression in mice. The simvastatin-induced up-regulation of ApoM was blocked by an HNF-1alpha inhibitor (UCDA) or an LXRalpha agonist (TO901317) in HepG2 cells which indicates that this effect is mediated via the regulation of HNF-1alpha and LXRalpha. In conclusion, simvastatin signi fi cantly up-regulated ApoM expression in vivo and in vitro, which indicates that ApoM is another novel apolipoprotein regulated by simvastatin. The mechanism of this effect is related to the regulation of HNF-1alpha and LXRalpha.