Department of Cadres Medical, Xiangya Hospital, Central South University, Changsha 410011, P.R. China.
Int J Mol Med. 2012 Mar;29(3):510-4. doi: 10.3892/ijmm.2011.853. Epub 2011 Dec 5.
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.
载脂蛋白 M（ApoM）是一种新近发现的人类载脂蛋白，主要存在于血浆中的高密度脂蛋白（HDL）中。他汀类药物对许多与 HDL 相关的载脂蛋白有影响。然而，他汀类药物是否对 ApoM 有影响尚不清楚。在本研究中，我们研究了辛伐他汀对 ApoM 表达的影响及其潜在机制。辛伐他汀在小鼠中上调肝 ApoM mRNA 和蛋白表达。在 HepG2 细胞中，辛伐他汀以剂量依赖性方式显著增强 ApoM mRNA 和蛋白表达。辛伐他汀增加了小鼠肝细胞核因子-1α（HNF-1α）mRNA 的表达，降低了肝 X 受体-α（LXRα）mRNA 的表达。在 HepG2 细胞中，HNF-1α 抑制剂（UCDA）或 LXRα 激动剂（TO901317）阻断了辛伐他汀诱导的 ApoM 上调，表明这种作用是通过调节 HNF-1α 和 LXRα 介导的。总之，辛伐他汀在体内和体外显著上调了 ApoM 的表达，表明 ApoM 是另一种受辛伐他汀调节的新型载脂蛋白。这种作用的机制与 HNF-1α 和 LXRα 的调节有关。
