Gene and microRNA transcriptional signatures of angiotensin II in endothelial cells.
Gene and microRNA transcriptional signatures of angiotensin II in endothelial cells.
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DOI：
10.1097/fjc.0000000000000118
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发表时间：
2015-02
影响因子：
3
通讯作者：
Khaidakov M
中科院分区：
文献类型：
--
作者：
Mehta JL;Mercanti F;Stone A;Wang X;Ding Z;Romeo F;Khaidakov M
补充数字内容在文本中可用。动脉粥样硬化斑块的生长需要新血管形成（血管生成）。为了阐明血管紧张素II（Ang II）参与血管生成，我们进行基因芯片和microRNA（miRNA）聚合酶链反应阵列分析人冠状动脉内皮细胞暴露于中等浓度的Ang II 2和12小时。在12小时，而不是2小时，用Ang II处理的培养物表现出涉及267个基因的转录活性的变化（>1.5倍差异; P < 0.05）。所得转录组最显著地富集与血管发育、血管生成和增殖调节相关的基因。大多数参与血管生成的上调基因都具有共同点，即是STAT 3的调节因子（HES 1、IL-18和CXCR 4）或靶点（ADM、ANPEP、HES 1、KIT、NOTCH 4、PGF和SOX 18）。与这些发现一致，STAT 3抑制减弱了基质胶测定中血管紧张素II依赖的管形成刺激。miRNA转录物的表达分析显示，miRNA的差异表达模式在很大程度上与促血管生成反应一致，其突出主题是靶向PTEN的miR（miR-19 b-3 p、miR-21- 5 p、23 b-3 p和24- 3 p）的上调，其中许多直接或间接依赖于STAT 3。我们的结论是，STAT 3信号可能是一个内在的一部分，血管紧张素II介导的促血管生成反应在人内皮细胞。
Supplemental Digital Content is Available in the Text. Growth of atherosclerotic plaque requires neovascularization (angiogenesis). To elucidate the involvement of angiotensin II (Ang II) in angiogenesis, we performed gene microarray and microRNA (miRNA) polymerase chain reaction array analyses on human coronary artery endothelial cells exposed to moderate concentration of Ang II for 2 and 12 hours. At 12, but not 2, hours, cultures treated with Ang II exhibited shifts in transcriptional activity involving 267 genes (>1.5-fold difference; P < 0.05). Resulting transcriptome was most significantly enriched for genes associated with blood vessel development, angiogenesis, and regulation of proliferation. Majority of upregulated genes implicated in angiogenesis shared a commonality of being either regulators (HES1, IL-18, and CXCR4) or targets (ADM, ANPEP, HES1, KIT, NOTCH4, PGF, and SOX18) of STAT3. In line with these findings, STAT3 inhibition attenuated Ang II–dependent stimulation of tube formation in Matrigel assay. Expression analysis of miRNAs transcripts revealed that the pattern of differential expression for miRNAs was largely consistent with proangiogenic response with a prominent theme of upregulation of miRs targeting PTEN (miR-19b-3p, miR-21-5p, 23b-3p, and 24-3p), many of which are directly or indirectly STAT3 dependent. We conclude that STAT3 signaling may be an intrinsic part of Ang II–mediated proangiogenic response in human endothelial cells.