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Open Access Research

The rhythmic expression of clock genes attenuated in human plaque-derived vascular smooth muscle cells

Changpo Lin1, Xiao Tang1, Zhu Zhu2, Xiaohong Liao2, Ran Zhao2, Weiguo Fu1, Bin Chen1, Junhao Jiang1, Ruizhe Qian2* and Daqiao Guo1*

Author Affiliations

1 Institute of Vascular Surgery, Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China

2 Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai 200032, China

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Lipids in Health and Disease 2014, 13:14  doi:10.1186/1476-511X-13-14

Published: 13 January 2014

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.

Conclusion

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.

Keywords:
Circadian rhythm; Primary cell culture; Human vascular smooth muscle cells; Atherosclerosis; Plaque rupture