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由氧化型低密度脂蛋白调控的内皮细胞长链非编码RNA

Endothelial long non-coding RNAs regulated by oxidized LDL.

作者信息

Singh Krishna K, Matkar Pratiek N, Pan Yi, Quan Adrian, Gupta Vijay, Teoh Hwee, Al-Omran Mohammed, Verma Subodh

机构信息

Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, M5B 1W8, Canada.

Division of Vascular Surgery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, 5E21 KRCBS, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.

出版信息

Mol Cell Biochem. 2017 Jul;431(1-2):139-149. doi: 10.1007/s11010-017-2984-2. Epub 2017 Mar 18.

Abstract

Oxidized low-density lipoprotein (oxLDL) plays a central role in the pathogenesis of atherosclerosis, in part via an effect to promote endothelial dysfunction. In the present study, we evaluated the expression profiles of long non-coding RNAs (lncRNAs) and protein-coding mRNAs in endothelial cells following oxLDL stimulation. LncRNAs and mRNAs from human umbilical vein endothelial cells (HUVECs) were profiled with the Arraystar Human lncRNA Expression Microarray V3.0 following 24 h of oxLDL treatment (100 µg/mL). Of the 30,584 lncRNAs screened, 923 were significantly up-regulated and 975 significantly down-regulated (P < 0.05) in response to oxLDL exposure. In the same HUVEC samples, 518 of the 26,106 mRNAs screened were up-regulated and 572 were down-regulated. Of these differentially expressed lncRNAs, CLDN10-AS1 and CTC-459I6.1 were the most up-regulated (87-fold) and down-regulated (28-fold), respectively. Bioinformatic assignment of the differentially regulated genes into functional groups indicated that many are involved in signaling pathways among which are the cytokine receptor, chemokine, TNF, MAPK and Ras signaling pathways, olfactory transduction, and vascular smooth muscle cell function. This is the first report profiling oxLDL-mediated changes in lncRNA and mRNA expression in human endothelial cells. The novel targets revealed substantially extend the list of potential candidate genes involved in atherogenesis.

摘要

氧化型低密度脂蛋白(oxLDL)在动脉粥样硬化的发病机制中起核心作用,部分原因是它会促进内皮功能障碍。在本研究中,我们评估了oxLDL刺激后内皮细胞中长链非编码RNA(lncRNA)和蛋白质编码mRNA的表达谱。在用oxLDL(100μg/mL)处理24小时后,使用Arraystar人类lncRNA表达微阵列V3.0对人脐静脉内皮细胞(HUVECs)中的lncRNA和mRNA进行分析。在筛选的30584种lncRNA中,有923种在oxLDL暴露后显著上调,975种显著下调(P<0.05)。在相同的HUVEC样本中,筛选的26106种mRNA中有518种上调,572种下调。在这些差异表达的lncRNA中,CLDN10-AS1和CTC-459I6.1分别是上调最多(约87倍)和下调最多(约28倍)的。将差异调节基因进行生物信息学分类到功能组表明,许多基因参与信号通路,其中包括细胞因子受体、趋化因子、TNF、MAPK和Ras信号通路、嗅觉转导以及血管平滑肌细胞功能。这是第一份分析oxLDL介导的人内皮细胞lncRNA和mRNA表达变化的报告。所揭示的新靶点大大扩展了参与动脉粥样硬化发生的潜在候选基因列表。

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