title: Differentially expressed microRNAs at different stages of atherosclerosis in ApoE-deficient mice.
abstract: BACKGROUND
  Atherosclerosis is the primary cause of cardiovascular disease, carotid artery disease, and peripheral vascular disease. However, it is hard to obtain human arterial tissue at different stages of atherosclerosis for a systematic study. The ApoE-deficient (ApoE(-/-)) mice predictably develop spontaneous atherosclerotic plaques with numerous features similar to the human lesions and contain nearly the entire spectrum of lesions observed during atherogenesis in humans. MicroRNA expression profiles at different stages of atherosclerosis in ApoE-deficient mice were screened to find out the differentially expressed microRNAs.
  
  
  METHODS
  ApoE-deficient mice were euthanized at 4, 8, and 20 weeks of age and divided into three groups according to the three time points, including groups A4 (fed a Western-type diet for 0 week), A8 (fed a Western-type diet for 4 weeks), and A20 (fed a Western-type diet for 16 weeks). Atherosclerotic lesions were analyzed. Fifteen aortas were collected and combined into three pools (five aortas in one pool) in each group. MicroRNA microarray analysis was replicated thrice in each group. The threshold of fold change ≥ 2.0 was used to screen up or down-regulated microRNAs. Differentially expressed microRNAs were subsequently verified with quantitative real-time polymerase chain reaction. Those increasingly up or down-regulated microRNAs during the progression of atherosclerosis were selected.
  
  
  RESULTS
  Atherosclerotic lesions first appeared in the aortic arch in group A8. Severe atherosclerotic lesions were observed in group A20. In group A8, seven MicroRNAs were up-regulated while two were down-regulated. In group A20, 15 microRNAs were up-regulated while two were down-regulated. miR-34a-5p and miR-497-5p were increasingly up-regulated, while miR-434-3p was progressively down-regulated when atherosclerosis progressed.
  
  
  CONCLUSIONS
  In this study, we described that microRNAs are differentially expressed at different stages of atherosclerosis in ApoE-deficient mice. Those increasingly up or down-regulated microRNAs during the progression of atherosclerosis may play an important role in the pathogenesis of atherosclerosis and provide us opportunities for investigating atherosclerosis from early to advanced stages.
authors: Laboratory of General Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors: Zhen
authors: Z
authors: Shan
authors: Chen
authors: C
authors: Yao
authors: Zi-lun
authors: ZL
authors: Li
authors: Yuan
authors: Y
authors: Teng
authors: Wen
authors: W
authors: Li
authors: Jin-song
authors: JS
authors: Wang
authors: Cai-sheng
authors: CS
authors: Ye
authors: Guang-qi
authors: GQ
authors: Chang
authors: Xue-ling
authors: XL
authors: Huang
authors: Xiao-xi
authors: XX
authors: Li
authors: Wen-jian
authors: WJ
authors: Wang
authors: Shen-ming
authors: SM
authors: Wang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001057:Apolipoproteins E; D035683:MicroRNAs