Intermittent and sustained hypoxia induce a similar gene expression profile in human aortic endothelial cells
Intermittent and sustained hypoxia induce a similar gene expression profile in human aortic endothelial cells
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DOI：
10.1152/physiolgenomics.00091.2009
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发表时间：
2010-05-04
影响因子：
4.6
通讯作者：
Shimoda, Larissa A.
中科院分区：
文献类型：
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作者：
Polotsky, Vsevolod Y.;Savransky, Vladimir;Shimoda, Larissa A.
Polotsky VY，Savransky V，Bevans-Fonti S，Reinke C，Li J，Grigoryev DN，Shimoda LA.间歇性和持续性低氧诱导人主动脉内皮细胞相似的基因表达谱。Physiol Genomics 41：306-314，2010.首次发表于2010年3月2日; doi：10.1152/physiolgenomics.00091.2009。阻塞性睡眠呼吸暂停可引起血管炎症和动脉粥样硬化，这归因于间歇性缺氧（IH）。最近的数据表明，IH，而不是持续缺氧（SH），激活HeLa细胞中的促炎基因。IH和SH对人主动脉内皮细胞（HAEC）基因表达谱的影响尚未进行比较。我们用16%和0%O（2）（IH）的交替流或4%O（2）（SH-4%）、8%O（2）（SH-8%）或16%O（2）（对照）的恒定流灌注培养基8小时。进行Illumina基因微阵列，随后通过实时PCR进行验证。通过ELISA测量培养基中的促炎细胞因子。IH和SH-4%均上调促炎基因，包括热休克蛋白90-kDa B1、肿瘤坏死因子超家族成员4和血小板反应蛋白1。在所有促炎基因中，只有IL-8 mRNA在IH期间显示出显著更高的表达水平（1.78倍），与SH-4%相比，但两种类型的低氧暴露引起培养基中IL-8和IL-6蛋白水平显著增加3至8倍。IH和SH-4%还上调抗氧化基因，包括血红素加氧酶-1和核因子（红细胞衍生2）样2（NRF 2），而受缺氧诱导因子1（HIF-1）调节的经典基因，例如内皮素和葡萄糖转运蛋白GLUT 1，没有被诱导。SH-8%诱导的基因表达和细胞因子分泌的变化与IH和SH-4%相似。总之，短时间暴露于IH和SH上调HAEC中的促炎和抗氧化基因，并以类似的方式增加促炎细胞因子IL-8和IL-6向培养基中的分泌。
Polotsky VY, Savransky V, Bevans-Fonti S, Reinke C, Li J, Grigoryev DN, Shimoda LA. Intermittent and sustained hypoxia induce a similar gene expression profile in human aortic endothelial cells. Physiol Genomics 41: 306-314, 2010. First published March 2, 2010; doi:10.1152/physiolgenomics.00091.2009.-Obstructive sleep apnea may cause vascular inflammation and atherosclerosis, which has been attributed to intermittent hypoxia (IH). Recent data suggest that IH, but not sustained hypoxia (SH), activates proinflammatory genes in HeLa cells. Effects of IH and SH on the gene expression profile in human aortic endothelial cells (HAEC) have not been compared. We perfused media with alternating flow of 16% and 0% O(2) (IH) or constant flow of 4% O(2) (SH-4%), 8% O(2) (SH-8%), or 16% O(2) (control) for 8 h. Illumina gene microarrays were performed, with subsequent verification by real-time PCR. Proinflammatory cytokines in the media were measured by ELISA. Both IH and SH-4% upregulated proinflammatory genes, including heat shock protein 90-kDa B1, tumor necrosis factor superfamily member 4, and thrombospondin 1. Among all proinflammatory genes, only IL-8 mRNA showed significantly higher levels of expression (1.78-fold) during IH, compared with SH-4%, but both types of hypoxic exposure elicited striking three-to eightfold increases in IL-8 and IL-6 protein levels in the media. IH and SH-4% also upregulated antioxidant genes, including heme oxygenase-1 and nuclear factor (erythroid-derived 2)-like 2 (NRF2), whereas classical genes regulated by hypoxia-inducible factor 1 (HIF-1), such as endothelin and glucose transporter GLUT1, were not induced. SH-8% induced changes in gene expression and cytokine secretion that were similar to those of IH and SH-4%. In conclusion, short exposures to IH and SH upregulate proinflammatory and antioxidant genes in HAEC and increase secretion of proinflammatory cytokines IL-8 and IL-6 into media in similar fashions.