[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 atherosclerotic 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, apolipoprotein B100 (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 AV (apoAV) 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 AI (apo AI), apolipoprotein F (apo F), peroxidase proliferator-activated receptor alpha (PPAR-alpha), liver X receptor alpha (LXRalpha), 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.


CONCLUSIONS
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.
Du
Hui-qin
HQ
College of Life Sciences, Shandong Normal University, Jinan 250014, China.
Yin
Miao
M
Ye
Hong-yan
HY
Shang
Yun-ju
YJ
Dai
Xue-dong
XD
Jing
Wen
W
Zhang
Liang
L
Xiao
Ning
N
Li
Ji-feng
JF
Pan
Jie
J
D000818:Animals; D001011:Aorta / Q000473:pathology; D000072040:Apolipoprotein A-V; D053299:Apolipoprotein B-100 / Q000096:biosynthesis* / Q000235:genetics; D001053:Apolipoproteins / Q000096:biosynthesis* / Q000235:genetics; D001054:Apolipoproteins A / Q000096:biosynthesis* / Q000235:genetics; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D018955:CD36 Antigens / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency
C499058:Apoa5 protein, mouse; D000072040:Apolipoprotein A-V; D053299:Apolipoprotein B-100; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001057:Apolipoproteins E; D018955:CD36 Antigens; D012333:RNA, Messenger; D011973:Receptors, LDL; C022205:apolipoprotein A-IV