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血管紧张素 II 诱导的内皮细胞长非编码和编码 RNA 的转录组学。

Transcriptomics of angiotensin II-induced long noncoding and coding RNAs in endothelial cells.

机构信息

Department of Medical Biophysics.

Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London.

出版信息

J Hypertens. 2022 Jul 1;40(7):1303-1313. doi: 10.1097/HJH.0000000000003140.

Abstract

OBJECTIVE

Angiotensin II (Ang II)-induced endothelial dysfunction plays an important role in the pathogenesis of cardiovascular diseases such as systemic hypertension, cardiac hypertrophy and atherosclerosis. Recently, long noncoding RNAs (lncRNAs) have been shown to play an essential role in the pathobiology of cardiovascular diseases; however, the effect of Ang II on lncRNAs and coding RNAs expression in endothelial cells has not been evaluated. Accordingly, we sought to evaluate the expression profiles of lncRNAs and coding RNAs in endothelial cells following treatment with Ang II.

METHODS

Human umbilical vein endothelial cells (HUVECs) were cultured and treated with Ang II (10-6 mol/l) for 24 h. The cells were then profiled for the expression of lncRNAs and mRNAs using the Arraystar Human lncRNA Expression Microarray V3.0.

RESULTS

In HUVECs following Ang II treatment, from a total of 30 584 lncRNA targets screened, 25 targets were significantly upregulated, while 69 were downregulated. In the same HUVECs samples, from 26 106 mRNA targets screened, 28 targets were significantly upregulated and 67 were downregulated. Of the differentially expressed lncRNAs, RP11-354P11.2 and RP11-360F5.1 were the most upregulated (11-fold) and downregulated (three-fold) lncRNAs, respectively. Assigning the differentially regulated genes into functional groups using bioinformatics reveals numerous genes involved in the nucleotide excision repair and ECM-receptor interaction.

CONCLUSION

This is the first study to profile the Ang II-induced differentially expressed lncRNAs and mRNAs in human endothelial cells. Our results reveal novel targets and substantially extend the list of potential candidate genes involved in Ang II-induced endothelial dysfunction and cardiovascular diseases.

摘要

目的

血管紧张素 II(Ang II)诱导的内皮功能障碍在心血管疾病的发病机制中起着重要作用,如全身性高血压、心肌肥厚和动脉粥样硬化。最近,长链非编码 RNA(lncRNA)已被证明在心血管疾病的病理生物学中起着至关重要的作用;然而,Ang II 对内皮细胞中 lncRNA 和编码 RNA 表达的影响尚未得到评估。因此,我们试图评估 Ang II 处理后内皮细胞中 lncRNA 和编码 RNA 的表达谱。

方法

培养人脐静脉内皮细胞(HUVEC)并用 Ang II(10-6mol/l)处理 24 小时。然后使用 Arraystar Human lncRNA Expression Microarray V3.0 检测 lncRNA 和 mRNA 的表达谱。

结果

在 Ang II 处理后的 HUVEC 中,在总共筛选的 30584 个 lncRNA 靶标中,有 25 个靶标显著上调,而 69 个靶标下调。在相同的 HUVEC 样本中,在筛选的 26106 个 mRNA 靶标中,有 28 个靶标显著上调,67 个靶标下调。在差异表达的 lncRNA 中,RP11-354P11.2 和 RP11-360F5.1 分别是上调(11 倍)和下调(三倍)最显著的 lncRNA。使用生物信息学将差异调节基因分配到功能组中,揭示了许多涉及核苷酸切除修复和 ECM-受体相互作用的基因。

结论

这是第一项研究人内皮细胞中 Ang II 诱导的差异表达 lncRNA 和 mRNAs 的研究。我们的研究结果揭示了新的靶点,并大大扩展了涉及 Ang II 诱导的内皮功能障碍和心血管疾病的潜在候选基因列表。

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