title: Effect of simvastatin on the expression and regulation mechanism of             apolipoprotein M.
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-1α (HNF-1α) mRNA and reduced liver X receptor-α (LXRα) mRNA expression in mice. The simvastatin-induced up-regulation of ApoM was blocked by an HNF-1α inhibitor (UCDA) or an LXRα agonist (TO901317) in HepG2 cells which indicates that this effect is mediated via the regulation of HNF-1α and LXRα. In conclusion, simvastatin signiﬁcantly 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-1α and LXRα.
authors.affiliation: Department of Cadres Medical, Xiangya Hospital, Central South                     University, Changsha 410011, P.R. China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.forename: Shuiping
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001053:Apolipoproteins / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D056945:Hep G2 Cells; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D000924:Anticholesteremic Agents; D001053:Apolipoproteins; D051538:Hepatocyte Nuclear Factor 1-alpha; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D019821:Simvastatin