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Effect of simvastatin on the expression and regulation mechanism of apolipoprotein M
1Department of Cadres Medical, Xiangya Hospital, Central South University, Changsha 410011, P.R. China.
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.
Insights
Simvastatin significantly increases apolipoprotein M (ApoM) expression in liver cells and in vivo. This effect is mediated by regulating hepatocyte nuclear factor-1α (HNF-1α) and liver X receptor-α (LXRα).
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Apolipoprotein M (ApoM) is a plasma protein primarily found in high-density lipoprotein (HDL).
- Statins are known to influence various HDL-associated apolipoproteins.
- The effect of statins on ApoM expression remains largely uncharacterized.
Purpose of the Study:
- To investigate the impact of simvastatin on ApoM expression.
- To elucidate the molecular mechanisms underlying simvastatin's effect on ApoM.
Main Methods:
- In vivo studies using mice to assess hepatic ApoM mRNA and protein levels.
- In vitro experiments with HepG2 cells to evaluate simvastatin's dose-dependent effects on ApoM.
- Analysis of regulatory factors including hepatocyte nuclear factor-1α (HNF-1α) and liver X receptor-α (LXRα) expression.
- Pharmacological inhibition/activation of HNF-1α and LXRα pathways.
Main Results:
- Simvastatin significantly up-regulated ApoM mRNA and protein expression in mouse liver and HepG2 cells.
- Simvastatin treatment led to increased hepatic HNF-1α mRNA and decreased LXRα mRNA in mice.
- Inhibition of HNF-1α or activation of LXRα counteracted the simvastatin-induced ApoM up-regulation in HepG2 cells.
Conclusions:
- Simvastatin demonstrably up-regulates ApoM expression both in vivo and in vitro.
- The mechanism involves the modulation of HNF-1α and LXRα signaling pathways.
- ApoM emerges as a novel apolipoprotein whose expression is influenced by simvastatin.
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