Intracellular high cholesterol content disorders the clock genes, apoptosis-related genes and fibrinolytic-related genes rhythmic expressions in human plaque-derived vascular smooth muscle cells.
Intracellular high cholesterol content disorders the clock genes, apoptosis-related genes and fibrinolytic-related genes rhythmic expressions in human plaque-derived vascular smooth muscle cells.
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细胞内高胆固醇含量扰乱人斑块来源的血管平滑肌细胞的时钟基因、凋亡相关基因和纤溶相关基因的节律表达
DOI：
10.1186/s12944-017-0500-z
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发表时间：
2017-07-10
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;Xu L;Qian R;Shi Z;Wang L;Cai T;Yan D;Fu W;Guo D
背景生物钟基因参与调节心血管功能，其表达异常会导致生物钟控制基因（clock-controlled gene，CCGs）的昼夜节律紊乱，导致动脉粥样硬化斑块的形成和破裂。我们的前期研究发现，人斑块源性血管平滑肌细胞（PVSMCs）中时钟基因的节律性表达减弱，但未能检测到下游CCGs的表达及其分子机制。本研究旨在探讨人正常颈动脉血管平滑肌细胞（NVSMCs）和PVSMCs中CCGs节律性表达的差异。此外，我们比较了两组之间的胆固醇和甘油三酯水平和时钟基因和CCGs expressions.MethodsSeven健康供体的正常颈动脉和19颈动脉斑块产生了可行的培养NVSMCs和PVSMCs的链接。通过实时定量PCR和Western-blot检测靶基因的表达水平。结果糖尿病相关基因和纤溶相关基因的昼夜表达紊乱。此外，PVSMCs中的胆固醇水平显著较高。胆固醇或氧化低密度脂蛋白（ox-LDL）处理后，NVSMCs的时钟基因表达受到抑制，时钟基因、凋亡相关基因和纤溶相关基因的节律性表达受到干扰，与PVSMCs相似。结论PVSMCs细胞内高胆固醇含量导致时钟基因和CCGs节律性表达紊乱。具体的分子机制有待进一步研究。
BackgroundThe clock genes are involved in regulating cardiovascular functions, and their expression disorders would lead to circadian rhythm disruptions of clock-controlled genes (CCGs), resulting in atherosclerotic plaque formation and rupture. Our previous study revealed the rhythmic expression of clock genes were attenuated in human plaque-derived vascular smooth muscle cells (PVSMCs), but failed to detect the downstream CCGs expressions and the underlying molecular mechanism. In this study, we examined the difference of CCGs rhythmic expression between human normal carotid VSMCs (NVSMCs) and PVSMCs. Furthermore, we compared the cholesterol and triglycerides levels between two groups and the link to clock genes and CCGs expressions.MethodsSeven health donors’ normal carotids and 19 carotid plaques yielded viable cultured NVSMCs and PVSMCs. The expression levels of target genes were measured by quantitative real-time PCR and Western-blot. The intracellular cholesterol and triglycerides levels were measured by kits.ResultThe circadian expressions of apoptosis-related genes and fibrinolytic-related genes were disordered. Besides, the cholesterol levels were significant higher in PVSMCs. After treated with cholesterol or oxidized low density lipoprotein (ox-LDL), the expressions of clock genes were inhibited; and the rhythmic expressions of clock genes, apoptosis-related genes and fibrinolytic-related genes were disturbed in NVSMCs, which were similar to PVSMCs.ConclusionThe results suggested that intracellular high cholesterol content of PVSMCs would lead to the disorders of clock genes and CCGs rhythmic expressions. And further studies should be conducted to demonstrate the specific molecular mechanisms involved.
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影响因子：
4.3
作者：
Mercer, John;Bennett, Martin
通讯作者：
Bennett, Martin
影响因子：
8.7
作者：
Boyle, JJ;Bowyer, DE;Bennett, MR
通讯作者：
Bennett, MR
影响因子：
4.5
作者：
Hou L;Lu C;Huang Y;Chen S;Hua L;Qian R
通讯作者：
Qian R
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
影响因子：
4.5
作者：
Lin C;Tang X;Zhu Z;Liao X;Zhao R;Fu W;Chen B;Jiang J;Qian R;Guo D
通讯作者：
Guo D
影响因子：
3.8
作者：
Fendler, Wojciech;Rizzo, Manfredi;Borowiec, Maciej;Malachowska, Beata;Antosik, Karolina;Szadkowska, Agnieszka;Banach, Maciej;Urbanska-Kosinska, Malgorzata;Szopa, Magdalena;Malecki, Maciej;Mlynarski, Wojciech
通讯作者：
Mlynarski, Wojciech