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Effects of simvastatin on apolipoprotein M in vivo and in vitro.

Zhang, Xiaoying; Mao, Shubing; Luo, Guanghua; Wei, Jiang; Berggren Söderlund, Maria LU ; Nilsson-Ehle, Peter LU and Xu, Ning LU (2011) In Lipids in Health and Disease 10.
Abstract
OBJECTIVE:

To investigate effects of lipid lowering drug, simvastatin, on apolipoprotein M expression in the hyperlipidemic mice and in hepatic cell line, HepG2 cells.



METHODS:

Swiss male mice were randomly divided into the high fat group and control group, and were intragastrically fed with 0.9% saline (control group) or lipid emulsion (high fat group) at the daily dosage of 15 ml/kg body weight, respectively. After 8 weeks feeding, the hyperlipidemic model was successfully induced and these hyperlipidemic mice were then randomly divided into three experimental groups: vehicle control group, high-dose simvastatin-treated group (100 mg/kg body weight), and low-dose simvastatin-treated group (10 mg/kg... (More)
OBJECTIVE:

To investigate effects of lipid lowering drug, simvastatin, on apolipoprotein M expression in the hyperlipidemic mice and in hepatic cell line, HepG2 cells.



METHODS:

Swiss male mice were randomly divided into the high fat group and control group, and were intragastrically fed with 0.9% saline (control group) or lipid emulsion (high fat group) at the daily dosage of 15 ml/kg body weight, respectively. After 8 weeks feeding, the hyperlipidemic model was successfully induced and these hyperlipidemic mice were then randomly divided into three experimental groups: vehicle control group, high-dose simvastatin-treated group (100 mg/kg body weight), and low-dose simvastatin-treated group (10 mg/kg body weight). Mice were dosed daily for 6 weeks of simvastatin before mice were sacrificed for determining serum lipid profile and apoM protein levels that was determined by using dot blotting analysis. Effects of simvastatin on apoM mRNA expression in the HepG2 cells were determined by real-time RT-PCR.



RESULTS:

Comparing to high fat model mice without simvastatin treatment, 100 mg/kg simvastatin could significantly increase serum total cholesterol (P < 0.05). Serum apoM levels, in all mice, were significantly lower in the mice at the age of 26 weeks than the mice at 12 weeks old (P < 0.05), which indicated that serum apoM levels were significantly correlated to the mice age. It demonstrated also that treatment of simvastatin did not influence serum apoM levels in these mouse model, although serum apoM levels were increased by about 13% in the 10 mg/kg simvastatin group than in the vehicle control group without simvastatin. In HepG2 cell cultures, simvastatin could significantly decrease apoM mRNA levels with dose- and time-dependent manners. At 10 μM simvastatin treatment, apoM mRNA decreased by 52% compared to the controls.



CONCLUSION:

The present study suggested that simvastatin, in vivo, had no effect on apoM levels in the hyperlipidemic mouse model. ApoM serum levels in mice were significantly correlated to the animal's age, whereas in cell cultures simvastatin does inhibit apoM expression in the HepG2 cells. The mechanism behind it is not known yet. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Lipids in Health and Disease
volume
10
publisher
BioMed Central
external identifiers
  • wos:000292967500001
  • pmid:21729290
  • scopus:79959824875
ISSN
1476-511X
DOI
10.1186/1476-511X-10-112
language
English
LU publication?
yes
id
8d8b58c6-3a33-422e-b396-b3c51ce7936f (old id 2058959)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21729290?dopt=Abstract
date added to LUP
2011-08-01 17:44:30
date last changed
2017-01-15 04:02:35
@article{8d8b58c6-3a33-422e-b396-b3c51ce7936f,
  abstract     = {OBJECTIVE:<br/><br>
To investigate effects of lipid lowering drug, simvastatin, on apolipoprotein M expression in the hyperlipidemic mice and in hepatic cell line, HepG2 cells.<br/><br>
<br/><br>
METHODS:<br/><br>
Swiss male mice were randomly divided into the high fat group and control group, and were intragastrically fed with 0.9% saline (control group) or lipid emulsion (high fat group) at the daily dosage of 15 ml/kg body weight, respectively. After 8 weeks feeding, the hyperlipidemic model was successfully induced and these hyperlipidemic mice were then randomly divided into three experimental groups: vehicle control group, high-dose simvastatin-treated group (100 mg/kg body weight), and low-dose simvastatin-treated group (10 mg/kg body weight). Mice were dosed daily for 6 weeks of simvastatin before mice were sacrificed for determining serum lipid profile and apoM protein levels that was determined by using dot blotting analysis. Effects of simvastatin on apoM mRNA expression in the HepG2 cells were determined by real-time RT-PCR.<br/><br>
<br/><br>
RESULTS:<br/><br>
Comparing to high fat model mice without simvastatin treatment, 100 mg/kg simvastatin could significantly increase serum total cholesterol (P &lt; 0.05). Serum apoM levels, in all mice, were significantly lower in the mice at the age of 26 weeks than the mice at 12 weeks old (P &lt; 0.05), which indicated that serum apoM levels were significantly correlated to the mice age. It demonstrated also that treatment of simvastatin did not influence serum apoM levels in these mouse model, although serum apoM levels were increased by about 13% in the 10 mg/kg simvastatin group than in the vehicle control group without simvastatin. In HepG2 cell cultures, simvastatin could significantly decrease apoM mRNA levels with dose- and time-dependent manners. At 10 μM simvastatin treatment, apoM mRNA decreased by 52% compared to the controls.<br/><br>
<br/><br>
CONCLUSION:<br/><br>
The present study suggested that simvastatin, in vivo, had no effect on apoM levels in the hyperlipidemic mouse model. ApoM serum levels in mice were significantly correlated to the animal's age, whereas in cell cultures simvastatin does inhibit apoM expression in the HepG2 cells. The mechanism behind it is not known yet.},
  articleno    = {112},
  author       = {Zhang, Xiaoying and Mao, Shubing and Luo, Guanghua and Wei, Jiang and Berggren Söderlund, Maria and Nilsson-Ehle, Peter and Xu, Ning},
  issn         = {1476-511X},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {Lipids in Health and Disease},
  title        = {Effects of simvastatin on apolipoprotein M in vivo and in vitro.},
  url          = {http://dx.doi.org/10.1186/1476-511X-10-112},
  volume       = {10},
  year         = {2011},
}