Up-Regulation of Cell Adhesion Molecule Genes in Human Endothelial Cells Stimulated by Lymphotoxin Alpha: DNA Microarray Analysis

Abstract

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.