title: The rhythmic expression of clock genes attenuated in human plaque-derived vascular smooth muscle cells.
abstract: BACKGROUND
  Acute myocardial infarction and stroke are more likely to occur in the early morning. Circadian pacemakers are considered to be involved in the process. Many peripheral tissues and cells also contain clock systems. In this study, we examined whether the primary cultured human plaque-derived vascular smooth muscle cells (VSMCs) process circadian rhythmicity; furthermore, we investigated the expression difference of clock genes between normal human carotid VSMCs and human plaque-derived VSMCs.
  
  
  METHODS
  Fifty-six human carotid plaques provided the atherosclerotic tissue, and 21 samples yielded viable cultured primary VSMCs. The normal carotid VSMCs were cultured from donors' normal carotids. The mRNA levels of the target genes were measured by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).
  
  
  RESULTS
  After serum shock, both types of cells showed clear circadian expressions of Bmal1, Cry1, Cry2, Per1, Per2, Per3 and Rev-erbα mRNA; meanwhile the Clock mRNA show a rhythmic expression in plaque-derived SMCs but not in normal carotid VSMCs. The expression levels of these main clock genes were significantly attenuated in human plaque-derived VSMCs compared with normal human carotid VSMCs. The rhythm of Bmal1 mRNA in plaque-derived VSMCs was changed.
  
  
  CONCLUSIONS
  The present results demonstrate that the human plaque-derived VSMCs possess different circadian rhythmicity from that of normal carotid VSMCs. The rhythm changes of clock genes in plaque-derived VSMCs may be involved in the process of atherosclerosis and finally promote the rupture of plaque.
authors.forename: Changpo
authors.initials: C
authors.lastname: Lin
authors.forename: Xiao
authors.initials: X
authors.lastname: Tang
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liao
authors.forename: Ran
authors.initials: R
authors.lastname: Zhao
authors.forename: Weiguo
authors.initials: W
authors.lastname: Fu
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Junhao
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Institute of Vascular Surgery, Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. rzqian@shmu.edu.cn.
authors.forename: Ruizhe
authors.initials: R
authors.lastname: Qian
authors.forename: Daqiao
authors.initials: D
authors.lastname: Guo
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056926:CLOCK Proteins / Q000235:genetics* / Q000378:metabolism; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002478:Cells, Cultured; D002940:Circadian Rhythm; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D056926:CLOCK Proteins; C538943:CLOCK protein, human