The rhythmic expression of clock genes attenuated in human plaque-derived vascular smooth muscle cells.
The rhythmic expression of clock genes attenuated in human plaque-derived vascular smooth muscle cells.
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人斑块来源的血管平滑肌细胞中时钟基因的节律表达减弱
DOI：
10.1186/1476-511x-13-14
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发表时间：
2014-01-13
影响因子：
4.5
通讯作者：
Guo D
中科院分区：
文献类型：
--
作者：
Lin C;Tang X;Zhu Z;Liao X;Zhao R;Fu W;Chen B;Jiang J;Qian R;Guo D
研究背景急性心肌梗死和脑卒中好发于清晨。昼夜节律起搏器被认为参与了这一过程。许多外周组织和细胞也含有时钟系统。在这项研究中，我们研究了是否原代培养的人斑块衍生的血管平滑肌细胞（VSMCs）的过程昼夜节律性;此外，我们调查了正常人颈动脉VSMCs和人斑块衍生的VSMCs.MethodsFifty-six人颈动脉斑块提供的动脉粥样硬化组织，和21个样品产生了可行的培养的原代VSMCs之间的时钟基因的表达差异。正常颈动脉VSMCs取自供体的正常颈动脉。结果血清休克后，两种细胞均出现Bmal 1、Cry 1、Cry 2、Per 1、Per 2、Per 3和Rev-erbα mRNA的昼夜节律性表达，而Clock mRNA在斑块源性平滑肌细胞中呈节律性表达，而在正常颈动脉VSMCs中无明显表达。与正常人颈动脉VSMCs相比，这些主要时钟基因的表达水平在人斑块源性VSMCs中显著减弱。Bmal 1 mRNA的节律性在斑块源性VSMCs中被改变。ConclusionThe目前的结果表明，人斑块源性VSMCs具有不同的昼夜节律性从正常颈动脉VSMCs。斑块源性VSMCs生物钟基因的节律性变化可能参与了动脉粥样硬化的过程，并最终促进斑块的破裂。
BackgroundAcute 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.MethodsFifty-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).ResultsAfter 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.ConclusionThe 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.