PMID- 18603823 OWN - NLM STAT- MEDLINE DCOM- 20080807 LR - 20190608 IS - 1880-3873 (Electronic) IS - 1340-3478 (Linking) VI - 15 IP - 3 DP - 2008 Jun TI - Up-regulation of cell adhesion molecule genes in human endothelial cells stimulated by lymphotoxin alpha: DNA microarray analysis. PG - 160-5 AB - 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. FAU - Suna, Shinichiro AU - Suna S AD - Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan. FAU - Sakata, Yasuhiko AU - Sakata Y FAU - Sato, Hiroshi AU - Sato H FAU - Mizuno, Hiroya AU - Mizuno H FAU - Nakatani, Daisaku AU - Nakatani D FAU - Shimizu, Masahiko AU - Shimizu M FAU - Usami, Masaya AU - Usami M FAU - Takashima, Seiji AU - Takashima S FAU - Takeda, Hiroshi AU - Takeda H FAU - Hori, Masatsugu AU - Hori M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Japan TA - J Atheroscler Thromb JT - Journal of atherosclerosis and thrombosis JID - 9506298 RN - 0 (Lymphotoxin-alpha) RN - 0 (Oligonucleotides) SB - IM MH - Atherosclerosis/metabolism/pathology MH - Cell Adhesion MH - Cells, Cultured MH - Endothelial Cells/*cytology MH - Endothelium, Vascular/pathology MH - *Gene Expression Regulation MH - Humans MH - Lymphotoxin-alpha/*pharmacology MH - Monocytes/cytology MH - Oligonucleotide Array Sequence Analysis/*methods MH - Oligonucleotides/chemistry MH - *Polymorphism, Genetic MH - Signal Transduction MH - Umbilical Veins/cytology MH - *Up-Regulation EDAT- 2008/07/08 09:00 MHDA- 2008/08/08 09:00 CRDT- 2008/07/08 09:00 PHST- 2008/07/08 09:00 [pubmed] PHST- 2008/08/08 09:00 [medline] PHST- 2008/07/08 09:00 [entrez] AID - JST.JSTAGE/jat/E553 [pii] AID - 10.5551/jat.e553 [doi] PST - ppublish SO - J Atheroscler Thromb. 2008 Jun;15(3):160-5. doi: 10.5551/jat.e553.