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大鼠动脉粥样硬化发展的全转录组学研究。

Global transcriptomic study of atherosclerosis development in rats.

作者信息

Chen Lei, Yao Hong, Hui Ji-Yuan, Ding Sheng-Hao, Fan Yi-Ling, Pan Yao-Hua, Chen Kai-Hong, Wan Jie-Qing, Jiang Ji-Yao

机构信息

Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, People's Republic of China.

Department of Cardiology, Longyan First Hospital affiliated to Fujian Medical University, Fujian 364000, People's Republic of China.

出版信息

Gene. 2016 Oct 30;592(1):43-48. doi: 10.1016/j.gene.2016.07.023. Epub 2016 Jul 16.

DOI:10.1016/j.gene.2016.07.023
PMID:27425867
Abstract

Atherosclerosis is a chronic disease of the arterial wall and a leading cause of death worldwide. Though the pathophysiology of atherosclerotic lesion formation has been studied, we still lack evidence of the global changes in the artery during atherosclerosis. In this report, we induced atherosclerosis in rats and conducted GeneChip analysis on carotid arteries with or without plaque formation. We found that molecular pathways underlying plaque formation in atherosclerosis were related to immune response, angiogenesis, cell proliferation, apoptosis and hypoxic microenvironments, suggesting that the pathophysiology of atherosclerosis is varied. In addition, we showed that three lncRNAs, GAS5, SNHG6 and Zfas1, were significantly increased in the plaque of atherosclerosis patients compared to normal people. A complex interaction of mRNA and lncRNA was identified in atherosclerosis. Our results provide a global transcriptomic network of atherosclerosis development in rats and possible targets that could lead to new clinical applications in the future.

摘要

动脉粥样硬化是一种动脉壁的慢性疾病,也是全球主要的死亡原因。尽管已经对动脉粥样硬化病变形成的病理生理学进行了研究,但我们仍然缺乏动脉粥样硬化期间动脉整体变化的证据。在本报告中,我们诱导大鼠发生动脉粥样硬化,并对有或没有斑块形成的颈动脉进行基因芯片分析。我们发现动脉粥样硬化斑块形成的分子途径与免疫反应、血管生成、细胞增殖、细胞凋亡和缺氧微环境有关,这表明动脉粥样硬化的病理生理学是多样的。此外,我们还表明,与正常人相比,动脉粥样硬化患者斑块中的三种长链非编码RNA(lncRNA),即生长停滞特异性转录本5(GAS5)、小核仁RNA宿主基因6(SNHG6)和锌指反义RNA1(Zfas1)显著增加。在动脉粥样硬化中发现了mRNA和lncRNA的复杂相互作用。我们的结果提供了大鼠动脉粥样硬化发展的整体转录组网络以及可能在未来带来新临床应用的潜在靶点。

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