[Expression profiles of lipid metabolism-related genes in liver of apoE(-/-)/LDLR(-/-) mice].

Objective To explore the relationship between the expression characteristics of lipid metabolism-related genes in the liver and early atheroselerotic lesions in apolipoprotein E and low density lipoprotein receptor gene double knockout(apoE~(-/-)/LDLR~(-/-))mice.Methods RT-PCR was used to detect the differential expression of lipid metabolism-related genes in the liver of apoE~(-/-)/LDLR~(-/-)and wild type(WT)mice.Serum total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol (LDL-C)and high-density lipoprotein cholesterol(HDL-C)level as well as aortic morphology were also analyzed.Results Among the 11 lipid metabolism-related genes,apolipoproteinB100(apoB100)mRNA levels were significantly higher in apoE~(-/-)/LDLR~(-/-)mice compared with WT mice.At 14 days,1,2 and 3 months of age,the level of mRNA expression were 1.55,1.47,1.50 and 2.42 folds of those of the age matched WT mice respectively.The fatty acid transporter(FAT/CD36)mRNA expression levels were higher in 14-day and 3-month old mice at 1.30 and 1.35 folds of those of the age matched WT mice, respectively.Apolipoprotein A Ⅳ(apoA Ⅳ)and Apolipoprotein A Ⅴ(apoA Ⅴ)mRNA levels were significantly down-regulated(0.89 fold decrease in 14-day,and 0.90 folds decrease in 3-month, respectively).The mRNA expression levels of apolipoprotein A Ⅰ(apo AⅠ),apolipoprotein F(apo F), peroxidase proliferator-activated receptor α(PPAR-α),liver X receptor α(LXRα),angiopoietin-like protein 3(ANGPTL3),acyl-coenzymeA oxidase 1(ACOX1)and carnitine palmitoyl transferase 1(CPT1) had no significant changes.Serum TC,TG and LDL-C were higher than those of age matched WT mice at 7, 2 and 30 folds,respectively.Furthermore,apoE~(-/-)/LDLR~(-/-)mice demonstrated typical early atherosclerotic lesions at sinus and root regions of aorta in an age dependent manner.Conclusion Alterations of the expression of lipid metabolism-related genes in liver play important roles in the development of AS in the apoE~(-/-)/LDLR~(-/-)mice at early ages.