Expression Characterization Of Lipid Metabolism-related Genes And Glucose Metabolism-related Genes In The Liver In Apolipoprotein E And Low Density Lipoprotein Receptor Double Knockout (apoE-/-/LDLR-/-) Mice

Atherosclerosis (AS) is the most common clinical cardiovascular disease, AS and coronary artery disease (CAD) are the leading causes of death in the world. In recent years, the incidence of this disease has an obvious upward trend in China. Due to the complex etiology, its pathogenesis has not been fully clear yet. There are a variety of theories about the pathogenesis of AS, but the areas that the theories concerned are different respectively, and they reflected the occurrence of AS. Nowadays, the study about the pathogenesis of AS has changed from the single factor to the muti-factor. Metabolic disorder of lipid and carbohydrate is the core of AS. Hyperlipidemia is an independent risk factor in the occurrence and the development of AS. Our primary experiments show that, the synergies between blood lipid transport, metabolic pathway disorder caused by several abnormal genes related to lipid metabolism and other risk factors play important role in the occurrence and the development of AS. At present, there are few reports of expression characterization of lipid metabolism-related genes and glucose metabolism-related genes in the liver in apolipoprotein E and low density lipoprotein receptor double knockout (apoE-/-/LDLR-/-) mice. In order to find the great significant impact factor and discuss the changes in the law of lipid metabolism-related genes and glucose metabolism-related genes in the early stage of AS, apoE-/-/LDLR-/- mice has been used as a model, to detected the differential expression of lipid metabolism-related and glucose metabolism-related key genes in the liver of apoE-/-/LDLR-/- and wild type (WT) mice with RT-PCR technique. 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.The results showed that: In 17 lipid metabolism-related genes dctected, apoE-/-/LDLR-/-mice compared with WT mice, the mRNA expression levels of apolipoprotein A I (apoA I), apolipoprotein A IV (apoA IV), apolipoprotein B100 (apoB100), angiopoietin-like protein 3 (Angptl 3), fatty acid transporter (FAT/CD36), glucose-regulated protein 78 (GRP 78), fatty acid synthase (FAS), scavenger receptor class A (SR-A), scavenger receptor class BI (SR-BI), liver X receptorα(LXRα), and peroxidase proliferator-activated receptorα(PPARα) mRNA expression levels have been up-regulated from 14-day to the 3-month old respectively. Apolipoprotein A V (apoA V) and stearoyl-CoA desaturase-1 (SCD1) mRNA expression levels have been down-regulated from 14-day to the 3-month old respectively. The mRNA expression levels of apolipoprotein A II (apoA II), apolipoprotein F (apoF), acyl-coenzymeA oxidase 1 (ACOX1), carnitine palmitoyl transferase I (CPTI) and medium-chain acyl-coenzyme A dehydrogenase (MCAD) have no significant changes.The mRNA expression levels of glucose metabolism-related key genes phosphoenolpyruvate carboxykinase (PEPCK) and Protein Kinase B (Akt/PKB) have no changed, significantly.ApoE-/-/LDLR-/- mice compared with age matched WT mice, the levels of serum TC and LDL-C levels were significantly higher, the growth continued to rise with aging. TC and LDL-C levels were higher than those of age matched WT mice about 7 and 30-fold, respectively, and have been maintained at a higher level. TG levels were higher than those of age matched WT mice about 2 folds and HDL-C levels were higher than those of age matched WT mice about 3-4 folds. Meanwhile, in apoE-/-/LDLR-/- mice, with the increase of age, typical early atherosclerotic lesions were observed at sinus and root regions of aorta.The mRNA levels of partial genes related to the lipid metabolism of the apoE-/-/LDLR-/- mice were significantly changed compared with the age matched WT mice. And this has a positive correlation with dyslipidemia and the development process of AS in aorta. The results suggest that changes in expression of lipid metabolism-related genes in liver are participate in the development of AS in young age of the apoE-/-/LDLR-/- mice.