Effect of oxLDL on the uptake and clearance rate of cholesterol in v-SMC originated from human apoA1 transgenic mice.
- Author:
Ying ZENG
1
;
Gaofeng ZHAO
;
Jun QIAN
;
Zongli WANG
;
Mingpeng SHE
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Apolipoprotein A-I; genetics; metabolism; Blotting, Northern; Cell Division; drug effects; Cells, Cultured; Cholesterol; pharmacokinetics; Dose-Response Relationship, Drug; Gene Expression; Humans; Lipoproteins, LDL; pharmacology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle, Smooth, Vascular; cytology; drug effects; metabolism; RNA, Messenger; genetics; metabolism; Reverse Transcriptase Polymerase Chain Reaction; Time Factors
- From: Chinese Medical Journal 2002;115(4):584-588
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo study the inhibition effect of oxLDL on the uptake and clearance of intra-cellular (3)H-cholesterol in v-SMC from the human-apoA1 transgenic mice (C57BL/6) and the changes in human-apoA1 mRNA expression in v-SMC from human apoA1 transgenic mice after oxLDL stimulation.
METHODSv-SMC originally isolated from human apoA1 transgenic mice connected with a recombined mouse metallothionein-I (MT-I) promoter was used, and the effect of oxLDL on the uptake and clearance of intracellular (3)H-cholesterol was studied in v-SMC of the transgenic and control mice respectively, the study of h-apoA I mRNA expression from v-SMC of the transgenic mice were done by RT-PCR and Northern blot.
RESULTSoxLDL (30 microg/ml) strongly promoted the SMC proliferation. No difference was found in (3)H-cholesterol uptake between nSMC and trSMC, and the uptake rates of both kinds of SMC rose 100% after oxLDL stimulation. The efflux rates of (3)H-cholesterol in trSMC were much higher than those of nSMC (40% - 50%). After oxLDL stimulation, the clearance rates fell by 28% and 10%, respectively, for nSMC and trSMC. The result of RT-PCR and Northern blot showed that h-apoA1 gene expression was markedly increased by the stimulation of oxLDL.
CONCLUSIONExpression of the h-apoA1 gene in C57BL/6 mice enables them to reduce the accumulation of cholesterol in v-SMC. The trSMC can alleviate the harmful effect of oxLDL due to the increase of h-apoA1 expression.