Up-regulation of cell adhesion molecule genes in human endothelial cells stimulated by Lymphotoxin alpha: DNA microarray analysis
Up-regulation of cell adhesion molecule genes in human endothelial cells stimulated by Lymphotoxin alpha: DNA microarray analysis
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DOI：
10.5551/jat.e553
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发表时间：
2008-06-01
影响因子：
4.4
通讯作者：
Hori, Masatsugu
中科院分区：
文献类型：
--
作者：
Suna, Shinichiro;Sakata, Yasuhiko;Hori, Masatsugu
背景我们最近报道了肿瘤坏死因子家族成员-人脐静脉内皮细胞和冠状动脉内皮细胞基因表达谱的变化用包含8，500个基因的高密度寡核苷酸阵列分析用LTA处理的小鼠。10 ng/mL的LTA刺激2 h可诱导与信号转导、细胞粘附和化学吸引相关的基因表达，如B细胞核因子κ轻链多肽基因增强子（NF κ B）、内皮细胞粘附分子1（endothelial adhesion molecule 1，ECAM）、内皮细胞粘附分子2（endothelial adhesion molecule 2，ECAM）和内皮细胞粘附分子1（endothelial adhesion molecule 1，ECAM（E-选择素）、血管细胞粘附分子1（VCAM 1）和单核细胞趋化蛋白1（MCP 1）（在HUVEC中分别为2.6、55.7、45.3和2.8倍，在HCAEC中分别为2.6、137.2、64.0和13.0倍）。实时荧光定量RT-PCR分析证实LTA可剂量依赖性地增加HUVEC和HCAEC中E-Selectin和VCAM 1的表达。结论：LTA可增加人内皮细胞中参与动脉粥样硬化或炎症过程的多种基因的表达，提示LTA在动脉粥样硬化的发生发展中起作用。
Background. We recently reported that the A252G polymorphism of the Lymphotoxin-alpha (LTA) gene, a member of the tumor necrosis factor family, is strongly related with the onset of acute myocardial infarction; however, the roles of LTA in the development of atherosclerosis remain unclear.Methods and Results: Changes in gene expression profile in cultured human umbilical vein (HUVEC) and coronary artery endothelial cells (HCAEC) treated with LTA were analyzed with high density oligonucleotide arrays comprised of 8,500 genes. LTA stimulation at 10 ng/mL for 2 hours profoundly induced gene expression associated with signal transduction, cell adhesion and chemoattraction, such as the nuclear factor of kappa light polypeptide gene enhancer in B-cells (NFkB), endothelial adhesion molecule 1 (E-Selectin), vascular cell adhesion molecule 1 (VCAM1), and monocyte chemotactic protein 1 (MCP1) (2.6, 55.7, 45.3 and 2.8 fold in HUVEC, and 2.6, 137.2, 64.0 and 13.0 fold in HCAEC, respectively). Quantitative real-time reverse transcriptase-polymerase chain reaction analysis confirmed that LTA increased the expressions of E-Selectin and VCAM1 in a dose-dependent manner both in HUVEC and HCAEC.Conclusion: LTA increased the expression of various genes involved in the process of atherosclerosis or inflammation in human endothelial cells, suggesting the roles of LTA in the development of atherosclerosis.