| Atherosclerosis (AS) is a complex multifactorial disease. Due to its high incidence, it has attracted man's considerable attention to study its mechanisms. The factors participated in the occurrence and the development of AS are from the artery wall partially, and also from the remote site through the circulatory system. However, the factors that come from the remote site may play more important effect on the early process of the AS, and the disorders of the lipid metabolism is an important foundation for the development of AS. The liver synthesizes and releases various kinds of enzyme for lipoprotein metabolism. It is the center of endogenous and exogenous lipid metabolism pathway, and plays an important balance role for the lipid metabolism. The liver is the important target organ to research the lipid metabolism.The apoE-deficient (apoE-/-) mice were generated by inactivating the apoE gene by targeting. ApoE-/- mice are considered to be one of the most relevant models for AS since they are hypertriglyceridemia and develop spontaneous atherosclerotic lesions. The analysis of AS in the apoE-/- mouse has shown that the sequential events involved in lesion formation in this model are strikingly similar to those in well-established larger animal models of AS and in humans.In order to study the differential expression of the genes related to the lipid metabolism in the early stage of AS in the young apoE-/- mice of different ages in normal chow diet. Genotypes of mice were identified by using multiplex polymerase chain reaction (multi-PCR) analysis. The semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR technology were used to analyze the expression level of the genes in the liver of the apoE-/- and age-matched wild type (WT) mice from 14 days to 3 months. The serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were assayed using COD-PAP and GPO-PAP methods. The serum apolipoprotein B100 (apoB100) levels were quantitated by immune turbidimetry. Hearts were serially sectioned at -15℃, stained with Sudan IV, and counterstained with light green. ApoE-/- mice compared with WT mice, the mRNA level of the apolipoprotein A I (apoA I) and the apolipoprotein A V (apoA V) changed prominently at 14-day old (P<0.05). The level of the apoA I was up regulated, the expression of the apoA V, however was down regulated; At the age of 1 months, the level of the apoB100 was higher than that of WT mice (P<0.05); The expression of the apolipoprotein A IV (apoA IV) was up regulated at the age of 2 months (P<0.05), and there was obvious lipid deposition in the aortic intima of the apoE-/- mice; The level of liver X receptorα(LXRα) was higher than that of WT mice at the age of 3 months (P<0.05), its target gene angiopoietin-like protein 3 (Angptl 3) was higher than WT mice, too; The expression of peroxisome proliferator-activated receptorα(PPARα) was higher than that of WT mice at the age of 2 months (P<0.05), its target genes the fatty acid translocase (FAT/CD36) and fatty acid synthase (FAS) were up regulated at 2- and 3-month-old, respectively. The mRNA level of the stearoyl-COA desalurase-I (SCD I) related to the lipid synthase and the fatty acidβ-oxidation was significantly down regulated at 3-month-old comparing with the age-matched WT mice. The expression of the lipoprteinlipase (LPL) related to the TG metabolism was lower than that of WT mice at the age of 14 days (P<0.05); The level of the glucose-regulated protein 78 (GRP78) that relates to the endoplasmic reticulum stress was higher than that of WT mice at the age of 1 months (P<0.05); The expression of other genes detected at the present study have no significant changes (P>0.05). The serum TC, TG, LDL-C and HDL-C levels were higher than that of age matched WT mice from 14 days to 3 months. ApoE-/- mice had a marked increase on serum apoB100 levels, consistent with the trend of the serum LDL-C levels and the mRNA levels of the apoB100 in the liver. The mRNA levels of partial genes related to the lipid metabolism of the apoE-/- mice were significantly changed compared with the WT mice. The results suggest these genes might be of some relevance to the complicated lipid metabolism network, and had effect on the early stage of atherogenesis.
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