Suna Shinichiro, Sakata Yasuhiko, Sato Hiroshi, Mizuno Hiroya, Nakatani Daisaku, Shimizu Masahiko, Usami Masaya, Takashima Seiji, Takeda Hiroshi, Hori Masatsugu
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
J Atheroscler Thromb. 2008 Jun;15(3):160-5. doi: 10.5551/jat.e553.
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.
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.
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.
我们最近报道，肿瘤坏死因子家族成员淋巴毒素-α（LTA）基因的A252G多态性与急性心肌梗死的发病密切相关；然而，LTA在动脉粥样硬化发展中的作用仍不清楚。
用包含8500个基因的高密度寡核苷酸芯片分析了用LTA处理的培养人脐静脉内皮细胞（HUVEC）和冠状动脉内皮细胞（HCAEC）中基因表达谱的变化。10 ng/mL的LTA刺激2小时可显著诱导与信号转导、细胞粘附和趋化作用相关的基因表达，如B细胞中κ轻链多肽基因增强子的核因子（NFkB）、内皮粘附分子1（E-选择素）、血管细胞粘附分子1（VCAM1）和单核细胞趋化蛋白1（MCP1）（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）。定量实时逆转录-聚合酶链反应分析证实，LTA在HUVEC和HCAEC中均以剂量依赖方式增加E-选择素和VCAM1的表达。
LTA增加了人内皮细胞中参与动脉粥样硬化或炎症过程的各种基因的表达，提示LTA在动脉粥样硬化发展中的作用。
